Nucleotide Excision Repair (Homo sapiens)

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17, 37, 40, 47, 68...20, 53, 60, 70, 953, 10, 11, 13, 16...18, 35, 527527, 45, 69, 8969, 85, 8985, 892, 2530121227, 45, 69, 8939, 28, 36, 53, 60...7, 20, 24, 51, 55...18, 35, 5257, 9820, 53, 60, 70, 956, 23, 41, 7427, 8925, 641, 22, 38, 46, 48...13, 14, 21, 35, 54...4, 15, 672, 253, 71, 8826, 32, 39, 43, 50...9, 28, 36, 73, 80...44, 57, 62, 9811, 13, 29, 49, 79...39, 50, 56, 7727, 8961618, 82, 88, 948989nucleoplasmUBC(533-608) ERCC8 UBC(609-684) GTF2H2 EP300 CUL4B CUL4B dsDNA with transcription bubble GTF2H4 PCNA Ub-595-UBC(533-608) PRPF19 POLD3 CUL4B ERCC2 POLR2I UBC(1-76) UBC(153-228) UBC(229-304) GTF2H4 UBC(609-684) XPA XPA CUL4A PAR-DDB2 PAR-DDB2 ISY1 Ub,p-S2,S5-POLR2A POLR2D CCNH EP300 UBC(77-152) ERCC3 UBC(153-228) POLR2I POLR2H UBC(381-456) UBC(381-456) UBC(305-380) RFC4 POLR2C UBB(77-152) XPC RAD23A UBB(1-76) POLR2D CUL4B UBC(77-152) POLR2L PAR-PARP2 (PCNA:POLD,POLE),(MonoUb:K164-PCNA:POLK):RPA:RFC:Incised DNA without lesionGTF2H5 POLR2L UBC(533-608) RPA1 POLR2J UBB(77-152) COPS2 GTF2H2 UBB(153-228) PPIE UBC(153-228) GTF2H5 UBC(77-152) POLR2J UVSSA UBB(153-228) UBC(609-684) Ub-63-UBB(1-76) RPA3 GTF2H3 UBC(153-228) UBB(153-228) UBC(533-608) UBB(153-228) POLR2J ERCC3 POLR2D UBC(305-380) UBC(77-152) TCEA1YY1 Open bubble damaged DNA template:trimmed nascent mRNA POLR2H ERCC1 K63polyUb:C87-UBE2N:UBE2V2POLR2E POLD2 UBC(381-456) PCNA HyperphosphorylatedRNA Pol II:DamagedDNAtemplate:nascentmRNAhybrid:TFIIH:ERCC6POLR2B MNAT1 XPA CCNH PRPF19 DDB1 GTF2H2 UBC(381-456) MNAT1 CUL4A PAR-DDB2 USP7 UBB(1-76) PIAS1,3RBX1 ERCC3 POLD3 ERCC5CUL4A Ub:XPC:RAD23:CETN2:Distorted dsDNA:UV-DDB:PARP1,PARP2ERCC4 SSB-dsDNA:trimmed nascent mRNA CDK7 UBB(1-76) RPA3 UBC(533-608) RFC5 Ub-XPC GTF2H1 POLR2L POLR2I UBC(229-304) UBC(457-532) Ub:ERCC1UBC(457-532) POLR2B GTF2H3 GPS1 UBA52(1-76) UBB(1-76) UBA52(1-76) POLR2H UBB(1-76) TC-NER incisioncomplex:5'-inciseddamaged DNA:trimmednascent mRNARFC1 POLD4 POLR2L GTF2H5 ERCC2 PPIE UBC(609-684) GTF2H5 ERCC3 ERCC3 Ub-215-UBC(153-228) UBC(229-304) Ub-XPC UBC(457-532) Ub,p-S2,S5-POLR2A GTF2H2 UVSSA POLE PPiUBB(77-152) POLE UBC(1-76) Ub-519-UBC(457-532) POLR2C GTF2H3 GTF2H2 UBC(609-684) UBC(229-304) CCNH XPA GTF2H1 CCNH UBC(609-684) ZNF830 GTF2H5 RPS27A(1-76) POLE4 p-S2,S5-POLR2A UBC(609-684) ERCC8 POLR2F UBC(77-152) RFC5 UBC(229-304) UBC(381-456) UBE2I-G93-SUMO2 Ub,p-S2,S5-POLR2A POLR2G POLR2K GTF2H1 RFC2 GTF2H2 XAB2 POLD2 RFC5 UBB(77-152) POLE3 POLR2F RPS27A(1-76) UBC(1-76) CUL4B POLR2L POLR2D POLR2I UBC(1-76) (PCNA:POLD,POLE),(MonoUb:K164-PCNA:POLK):RPA:RFCPOLR2C PARP1,PARP2 dimersCETN2 ERCC3 GTF2H2 RPA1 RPS27A(1-76) PAR-PARP1 UBA52(1-76) POLE POLR2K ERCC6 UBA52(1-76) POLR2E POLR2G GTF2H4 UBC(457-532) UBE2N:UBE2V2TC-NERpost-incisioncomplex:incisedDNAwithoutlesion:trimmednascentmRNA:PCNA:(PCNA:POLD,POLE),(MonoUb:K164-PCNA:POLK):RPA:RFCUb-XPC POLR2C ERCC3 POLE SUMO1-C93-UBE2I POLE4 POLR2H GTF2H1 UBC(457-532) UBC(77-152) ERCC4 HMGN1 ERCC1 GTF2H4 UBC(1-76) UBC(609-684) GTF2H4 CUL4A XPA MNAT1 RAD23B RPS27A(1-76) XAB2 CUL4B DDB1 POLR2F POLR2B Ubiquitinated,hyperphosphorylated RNA Pol II:Damaged DNA template:nascent mRNA hybrid:TFIIH:Ub:ERCC6:ERCC8:DDB1:CUL4:RBX1ZNF830 UbGTF2H5 UBC(1-76) ISY1 Ub-XPC POLR2G GTF2H4 RFC5 UBC(229-304) POLR2C PAR-PARP1 PPIE UBC(457-532) CHD1L GTF2H2 POLR2D GG-NER incisioncomplex:5'-inciseddamaged DNACUL4A DDB1 UBC(609-684) UBC(305-380) RPA2 POLR2J UBB(77-152) GTF2H2 UBB(153-228) TCEA1 AQR GTF2H1 EP300 CDK7 CUL4A GTF2H2 GTF2H4 UBC(457-532) PAR-PARP2 POLR2H POLE3 RBX1 POLD,POLE,POLKRPS27A(1-76) H2OUb-367-UBC(305-380) TCEA1 GTF2H3 POLD3 RBX1 CHD1L UBB(1-76) Ub-63-UBB(1-76) DamageddsDNAwithopentranscriptionbubble:Hyperphosphorylated RNA Pol II:TFIIHUBA52(1-76) UBC(153-228) UBC(153-228) UBB(1-76) POLR2G HMGN1 UBA52(1-76) ACTR8 DDB1 GTF2H1 GTF2H5 PAR-DDB2 POLR2J UBB(153-228) GTF2H2 PAR-PARP2 POLD3 Ub,p-S2,S5-POLR2A UBC(229-304) CCNH ERCC2 UBC(381-456) Ub-215-UBB(153-228) POLR2L PAR-PARP1 UBC(533-608) HMGN1 CDK7 CUL4B MonoUb-K164-PCNA RFC1 UBC(305-380) POLR2J UBB(153-228) UBC(229-304) ERCC2 DDB2 ZNF830 UBC(457-532) POLD4 PRPF19 ERCC5 COPS5 AQR ISY1 RPS27A(1-76) RPA3 UBB(153-228) TCEA1 CUL4A LIG1 GTF2H1 ERCC3 XAB2 Damaged dsDNA with open transcription bubble ERCC3 POLR2E GTF2H3 PAR-PARP2 ERCC1 ERCC6 PRPF19 MonoUb-K164-PCNA ERCC6 UBC(1-76) RPA2 UBC(153-228) CHD1LERCC1 GTF2H4 ERCC6 UBB(77-152) UBC(533-608) K63polyUb-C87-UBE2N UBC(533-608) ERCC3 RFC2 UVSSA UBC(533-608) RFC3 UBC(229-304) POLD4 UBC(457-532) RAD23A PAR-DDB2 RBX1 RFC3 UVSSA RFC4 UBC(305-380) POLD1 RBX1 CDK7 GTF2H4 GTF2H4 UBC(229-304) RBX1 COPS7A COP9 signalosomeUBC(457-532) ZNF830 ERCC2 ERCC3 RPA1 XPA GTF2H1 POLK CUL4B UBC(229-304) Ub-215-UBC(153-228) PAR-DDB2 UBC(305-380) RFC4 UBC(457-532) UBC(229-304) SUMO2 UBC(533-608) PRPF19 UBC(305-380) PAR-PARP2 RPA1 POLR2L UBC(533-608) POLR2I ribonucleosidetriphosphateERCC3 UBC(1-76) GTF2H1 GTF2H3 UBB(77-152) UBC(77-152) UBC(533-608) Ub-519-UBC(457-532) ISY1 GTF2H1 UBB(153-228) POLR2K RBX1 UBC(1-76) UBC(609-684) RPA heterotrimerXAB2 UBB(77-152) GG-NERincisioncomplex:5'-inciseddamagedDNA:(PCNA:POLD,POLE),(MonoUb:K164-PCNA:POLK):RPA:RFCXAB2 Ub-ERCC6 damaged DNA substrate:nascent mRNA hybrid COPS8 UBC(533-608) MNAT1 UBC(457-532) UBC(457-532) UBC(153-228) POLR2F POLR2B GTF2H5 GTF2H5 UBB(153-228) RFC5 RFC1 USP45INO80B UBC(229-304) RPA1 GTF2H5 Ub-291-UBC(229-304) POLR2G XAB2 POLR2D ISY1 GTF2H1 RFC2 RBX1 ERCC2 RPA3 COPS3 POLR2H GTF2H5 POLR2J UBA52(1-76) UBC(229-304) POLK Ub-63-RPS27A(1-76) POLR2L ERCC8 GTF2H3 ISY1 Ub-139-UBC(77-152) PAR-PARP1 CETN2 UBB(153-228) UBC(77-152) Ub:XPC:RAD23:CETN2:Distorted dsDNA:PAR-UV-DDB:TFIIH:PAR-PARP1,PAR-PARP2PPIE CUL4B GTF2H5 damaged DNA substrate:nascent mRNA hybrid RBX1 POLD4 CUL4A DDB1 ERCC3 PRPF19 GTF2H2 UBC(457-532) COPS4 RPA3 CUL4A RPA2 ISY1 UBC(457-532) POLR2F TCEA1 POLE2 UBC(533-608) UBB(153-228) POLR2F RPS27A(1-76) CAKCUL4A Piincised DNA without lesion:trimmed nascent mRNA POLR2E POLR2K PPIE POLD1 UBC(229-304) UBC(305-380) UBB(77-152) POLR2E ERCC8 MonoUb-K164-PCNA MNAT1 ERCC2 UBB(77-152) UBC(381-456) UBC(381-456) PPIE XAB2 UBB(77-152) GTF2H3 UBC(381-456) PAR-PARP1 RPS27A(1-76) POLR2L Ub-671-UBC(609-684) UBC(1-76) PCNA POLR2J POLR2G ERCC3 RBX1 UBC(153-228) UBC(153-228) COPS8 PiPOLR2F XPA UBB(153-228) UBC(457-532) HMGN1 CCNH POLD3 UBA52(1-76) RPS27A(1-76) (PCNA:POLD,POLE),(MonoUb:K164-PCNA:POLK):RPA:RFC:SSB-dsDNAUBC(1-76) USP7 MNAT1 UBB(153-228) mRNARAD23B COPS7A Ub,p-S2,S5-POLR2A UBC(1-76) CETN2 POLR2F ISY1 CETN2 INO80 complexUBC(229-304) XRCC1 UBC(305-380) Distorted dsDNA RPA2 MonoUb-K164-PCNA GTF2H4 RPS27A(1-76) RPS27A(1-76) Ub-XPC ERCC3 TC-NERpost-incisioncomplex:SSB-dsDNA:trimmed nascent mRNA: (PCNA:POLD,POLE), (MonoUb:K164-PCNA:POLK):RPA:RFCRAD23A POLR2D RPA1 RPA2 PAR-PARP1 ERCC2 GTF2H1 ERCC6 UBC(153-228) CCNH DDB1 UBC(153-228) UBC(1-76) PAR-PARP1 PAR-DDB2 damaged DNA with 5' incision GTF2H4 UBB(1-76) RPS27A(1-76) H2OUBB(153-228) CHD1L GTF2H3 DDB2 TC-NER pre-incisioncomplexPOLR2C UBC(77-152) RPA1 POLR2I UBC(1-76) TCEA1 ERCC3 GTF2H5 UBB(77-152) AQR POLR2D CDK7 POLE2 UBB(77-152) UBC(381-456) POLR2C UBC(609-684) RFC3 CETN2 RFC5 RFC5 UBC(533-608) ERCC1 UBB(1-76) ERCC5 POLR2F UBC(609-684) Partially open bubble damaged DNA template:trimmed nascent mRNA MCRS1 GTF2H3 UBB(77-152) UBB(153-228) PPiRAD23A UBB(77-152) UBC(153-228) UBA52(1-76) SSB-dsDNA CUL4B UBC(305-380) UBB(153-228) POLR2K DDB1 DDB1 POLR2K Ub-595-UBC(533-608) CUL4B PRPF19 ERCC5 GTF2H3 PCNA AQR DDB1 UBC(1-76) UBA52(1-76) GTF2H3 RPA1 UBC(533-608) UBC(1-76) UBB(77-152) UbUBC(229-304) RFC1 CCNH AQR UBB(153-228) RPA3 UBC(1-76) RFC3 POLR2E ERCC8 UBC(229-304) COPS7B Ub:ERCC6GTF2H2 GTF2H3 UBC(609-684) Ub-63-UBA52(1-76) POLE ERCC3 POLD2 UBC(1-76) UBC(609-684) PRPF19 POLR2E POLR2H UBB(1-76) Open bubble damaged DNA template:trimmed nascent mRNA TCEA1 SUMO2-C93-UBE2I POLR2G POLR2D ERCC3 POLE2 GTF2H1 ERCC3 Ub-63-UBC(1-76) POLR2E POLD1 POLR2C GTF2H1 POLR2G damaged DNA with open bubble structure RPS27A(1-76) POLR2D Ub-ERCC1 ERCC2 RBX1 RPS27A(1-76) TC-NERpre-incisioncomplex:OpenbubbledamagedDNAtemplate:RPA:ERCC5:trimmed nascent mRNAGTF2H1 COPS7B GTF2H2 PPIE UBC(305-380) UBB(1-76) POLE3 USP7 INO80E Ub:XPC:RAD23:CETN2:Open bubble-dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1,PAR-PARP2:CHD1LERCC2 GTF2H1 SUMO1 POLR2L POLR2H RPA2 RPA2 GTF2H1 POLE2 UBC(77-152) ISY1 ERCC1 DDB1 UBC(609-684) UBC(229-304) UBC(305-380) UBC(1-76) LIG3 UBC(153-228) UBC(457-532) RPA2 UBC(533-608) POLR2L UBC(153-228) POLE UBC(381-456) POLE3 CCNH RPS27A(1-76) UBC(229-304) CCNH UBC(457-532) POLR2J POLE4 GTF2H4 UBB(153-228) CUL4A DDB1 UBB(1-76) CHD1L POLD2 UBC(381-456) UBC(305-380) CDK7 POLD1 POLR2F RPA3 ISY1 ERCC3 CUL4A CETN2 CUL4A UBC(77-152) UBC(153-228) damaged DNA substrate:nascent mRNA hybrid RPA1 UBA52(1-76) POLR2D MNAT1 CUL4B NAD+UBB(153-228) RPS27A(1-76) GTF2H5 UBC(305-380) RAD23A Ub,SUMO,K63polyUb:XPC:RAD23:CETN2RBX1 UBC(305-380) PAR-PARP1 POLR2L ATPRPS27A(1-76) CUL4A XPA POLR2E RFC3 POLR2E ERCC2 POLR2G UBB(77-152) RUVBL1 Ub,SUMO:XPC:RAD23:CETN2:Open bubble-dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1, PAR-PARP2:CHD1LERCC8 CDK7 UBC(457-532) CUL4B RBX1 UBC(153-228) POLR2C UBA52(1-76) RPS27A(1-76) POLR2J ERCC3 CDK7 RAD23B UBC(77-152) POLR2C GTF2H3 UBC(609-684) CUL4A UBC(77-152) DDB1 damaged DNA with open bubble structure PAR-PARP2 Ub-63-UBA52(1-76) UBC(533-608) UBB(77-152) UBB(1-76) GTF2H2 UBC(609-684) dsDNAUBC(305-380) UBC(229-304) UBC(1-76) UBC(77-152) AQR CDK7 COPS6 POLD,POLE ERCC2 XAB2 HMGN1 UBC(381-456) UBA52(1-76) GTF2H2 ZNF830 GTF2H5 MNAT1 UBC(77-152) RPS27A(1-76) UBB(1-76) GTF2H1 POLR2G RAD23B COPS6 UBC(229-304) UBC(533-608) GTF2H1 POLR2J UBC(305-380) POLR2I POLR2A UBE2V2 GTF2H1 POLR2F UBC(77-152) POLR2D XPA RPA3 Distorted dsDNA POLR2F UBC(1-76) USP7 UBC(305-380) CCNH CUL4B POLK CDK7 UBA52(1-76) CHD1L p-S2,S5-POLR2A RFC2 POLR2F GTF2H5 UBC(609-684) PAR-PARP2 POLR2H GTF2H2 PAR-PARP1 DDB1 POLR2B UBB(1-76) damaged DNA substrate:nascent mRNA hybrid GTF2H1 AQR POLR2I ERCC3 GTF2H5 GTF2H2 RAD23RPA2 UBC(229-304) DDB1 RBX1 MonoUb-K164-PCNA GTF2H3 GTF2H1 GTF2H2 UBA52(1-76) GTF2H1 UBC(77-152) XAB2 RFC HeteropentamerPOLD3 UBC(229-304) GTF2H5 ERCC6 TCEA1 GTF2H3 RPA2 PAR-DDB2 TCEA1 ERCC8:DDB1:CUL4:RBX1:COP9 SignalosomeUBE2I-G92-SUMO3 RBX1 RFC3 EP300 RBX1 MNAT1 Open bubble damaged DNA template:trimmed nascent mRNA DDB1 UBC(77-152) RFC2 Distorted dsDNA UBB(153-228) Ub-XPC UVSSA POLR2B GTF2H3 PIAS3 UBC(1-76) GTF2H1 GTF2H4 RAD23B GTF2H5 UBC(533-608) PAR-DDB2 UBC(533-608) CUL4B POLR2L UBC(305-380) USP7 RNA Polymerase IIholoenzyme complex(unphosphorylated)GTF2H1 RPA3 CUL4B CUL4A PPIE POLR2H CDK7 NFRKB UBC(153-228) UBC(533-608) POLR2G UBB(1-76) POLK UBC(77-152) ZNF830 ATPPOLR2G ERCC2 POLE3 GTF2H2 CUL4A POLR2E UBC(381-456) GTF2H3 UBA52(1-76) POLR2F AQR CETN2COPS5 DDB1 GTF2H4 UBC(609-684) RPA3 NAMRBX1 GTF2H5 UBB(1-76) PAR-DDB2 RPA1 CUL4A POLE RPA1 DDB1 RAD23B PRPF19 PAR-PARP1 DDB1 ISY1 UBC(381-456) RBX1 UBC(381-456) Distorted dsDNA ERCC6 POLR2D DDB1 UBC(609-684) DDB2 Ub,p-S2,S5-POLR2A UBC(229-304) UBC(457-532) RPA3 UBC(609-684) COPS8 MNAT1 RPS27A(1-76) XAB2 POLR2J RPA3 RFC1 UBC(381-456) CUL4A UBA52(1-76) ZNF830 XPCCETN2 UBB(153-228) POLR2K POLR2H CCNH XPA POLD2 Ub,p-S2,S5-POLR2A UBC(609-684) POLR2B UBC(381-456) ERCC3 COPS2 ERCC2 HMGN1 UBC(457-532) POLD1 USP7 Ub-671-UBC(609-684) GTF2H4 CUL4B ADPUb,p-S2,S5-POLR2A UBB(153-228) CDK7 UBB(77-152) ERCC8 CUL4A UBA52(1-76) UBC(457-532) POLR2F MonoUb-K164-PCNA ERCC2 CHD1L UBC(305-380) DDB1 UBC(457-532) UBC(305-380) POLR2C UBC(609-684) Ub-ERCC6 ADPPOLD2 CUL4A LIG1,LIG3:XRCC1POLR2K GTF2H3 USP7 GTF2H5 ERCC4 POLR2K Distorted dsDNA incised DNA without lesion POLR2B SUMO3 GTF2H4 RAD23B PPiPOLR2K POLR2B POLR2F CETN2 CUL4A UBB(77-152) GTF2H4 RBX1 CUL4B UBC(533-608) UBC(533-608) RAD23A DDB1 POLR2H damaged DNA substrate:nascent mRNA hybrid ERCC5 UBC(229-304) XPA damaged DNA with open bubble structure POLR2B GTF2H3 UBC(609-684) GTF2H3 GPS1 PAR-PARP2 POLR2B Ub-443-UBC(381-456) POLR2D UBC(381-456) MNAT1 CUL4B ERCC1:ERCC4CUL4B RPS27A(1-76) POLR2K ERCC8 TC-NER pre-incisioncomplex:Partiallyopen bubble damagedDNAtemplate:trimmednascent mRNAEP300 COPS2 Ub-ERCC6 CUL4A UBC(153-228) POLR2C UBC(533-608) UBC(533-608) ERCC2 TFPT HMGN1 POLE3 UVSSA DDB1 UBC(305-380) CUL4B RPS27A(1-76) UBC(457-532) POLR2I UBC(457-532) GTF2H4 UBC(77-152) CUL4B RPS27A(1-76) UVSSA PAR-PARP1,PAR-PARP2dimersPAR-PARP1 UBC(77-152) UBC(1-76) Ub-63-RPS27A(1-76) EP300 damaged DNA substrate:nascent mRNA hybrid XPC UBC(457-532) AQR ZNF830 COPS6 ERCC2 PPIE ERCC2 5'-incised damaged DNA:trimmed nascent mRNA GTF2H3 UBC(533-608) CUL4B UBA52(1-76) UBB(1-76) MNAT1 RBX1 CUL4B PAR-PARP2 POLR2I EP300 RNAPolymeraseIIholoenzymecomplex(hyperphosphorylated)CUL4B ERCC6 UBB(1-76) UBC(533-608) XAB2 complexUBC(381-456) RFC4 UBC(305-380) ERCC2 ZNF830 RBX1 POLR2J PAR-PARP2 PAR-DDB2 PAR-PARP2 CDK7 UBC(457-532) EP300 GTF2H2 POLR2E XPC:RAD23:CETN2UBC(381-456) CUL4B POLR2H 5'-incised damaged DNA:trimmed nascent mRNA Ubiquitinated,hyperphosphorylated RNA Pol II:Damaged DNA template:nascent mRNA hybrid:TFIIH:Ub:ERCC6:ERCC8:DDB1:CUL4:RBX1:UVSSA:USP7:XAB2 complex:XPA:TCEA1:HMGN1:EP300RPA1 RPS27A(1-76) PPIE Ub:XPC:RAD23:CETN2:Distorted dsDNA:UV-DDBRBX1 UBC(457-532) UBB(153-228) RPS27A(1-76) POLR2C MNAT1 UBC(153-228) GTF2H2 ZNF830 COPS3 UBC(1-76) POLR2E CUL4A ERCC3 ERCC8 CUL4A UBE2I-G97-SUMO1 POLR2J DDB1 HMGN1POLR2L RBX1 UBC(609-684) USP7 GTF2H3 PCNA ERCC8 CUL4A UBC(229-304) CCNH GTF2H5 UVSSA:USP7CUL4B POLR2J GTF2H2 SUMO2 GTF2H3 HyperphosphorylatedRNAPolII:DamagedDNAtemplate:nascentmRNAhybrid:TFIIH:ERCC6:ERCC8:DDB1:CUL4:RBX1CETN2 RPA1 ERCC4 UBB(77-152) POLE4 ERCC8 RBX1 ERCC8 XPA POLK POLR2C RPS27A(1-76) UBC(305-380) ERCC5 POLR2C RFC3 POLE2 ERCC2 UBC(305-380) POLR2G POLD4 UBC(533-608) GTF2H5 UBA52(1-76) POLE2 UBB(1-76) UBB(1-76) GTF2H4 ERCC8 GTF2H4 ELLGTF2H3 XPAUBB(1-76) UBC(153-228) RPA3 GTF2H5 PRPF19 CDK7 UBC(153-228) GTF2H2 POLK RFC1 UBB(1-76) POLR2B ERCC2 UBC(533-608) UBC(381-456) INO80C UBB(77-152) UV-DDB:COP9SignalosomeRBX1 UVSSA POLR2K POLR2L RPS27A(1-76) GTF2H4 RPA3 ZNF830 POLE4 EP300 POLR2I UBC(77-152) RFC5 RBX1 UBC(229-304) UBC(1-76) RAD23A UBB(1-76) CCNH POLR2B POLR2D POLR2G RNF111RBX1 RAD23B damaged DNA with open bubble structure INO80 UBC(609-684) RBX1 UBB(1-76) UBC(381-456) UBC(77-152) POLR2D POLR2B UBB(77-152) UBC(153-228) PCNA EP300 RFC4 PARP2 p-S2,S5-POLR2A RPS27A(1-76) UBC(457-532) PAR-UV-DDBUb:XPC:RAD23:CETN2:Distorted dsDNA:PAR-UV-DDB:PAR-PARP1,PAR-PARP2RPS27A(1-76) p-S2,S5-POLR2A TC-NERincisioncomplex:5'-inciseddamagedDNA:trimmednascentmRNA:(PCNA:POLD,POLE), (MonoUb:K164-PCNA:POLK):RPA:RFCERCC1UBC(1-76) UBC(381-456) POLR2K CETN2 POLR2H CCNH POLR2L POLD1 ERCC6 UVSSA ERCC3 UBC(77-152) POLR2H UBA52(1-76) UBB(77-152) UBC(1-76) POLR2K UBC(381-456) INO80D GTF2H5 PRPF19 UBC(77-152) damaged DNA with open bubble structure USP7 UBC(153-228) POLR2I RBX1 TFIIHCUL4B ERCC2 CETN2 XAB2 PPIE HMGN1 GTF2H4 POLR2I Ub,p-S2,S5-POLR2A PAR-DDB2 TFIIH CoreXPA RPS27A(1-76) UBC(153-228) UBC(609-684) UBA52(1-76) GTF2H4 POLR2L ERCC6 RFC2 HMGN1 UBC(457-532) ATPRPS27A(1-76) POLR2I Ub-443-UBC(381-456) POLR2H UBC(1-76) GTF2H2 PARP1 UBC(457-532) CUL4A UBC(305-380) CDK7 UBC(153-228) TC-NER incisioncomplexUBC(305-380) POLR2J ERCC6 UBB(1-76) CDK7 MNAT1 UBA52(1-76) RFC4 XPA DDB1 COPS7B dNTPGG-NER incisioncomplex:Open bubbledsDNACUL4A POLR2K CHD1L ERCC2 UBB(77-152) USP7 UBA52(1-76) EP300 UBC(381-456) ERCC5 ERCC4 UBB(77-152) ERCC1 UbDDB1 UBC(305-380) PCNA RPA2 RAD23A RPA2 ERCC8 RPA2 MNAT1 UBB(77-152) UBC(381-456) TCEA1 POLR2C CCNH ERCC3 POLR2E POLR2D p-S2,S5-POLR2A UBC(1-76) COPS4 UBC(229-304) ERCC3 CUL4A XPA UBB(153-228) POLR2E ERCC4ERCC2 UBA52(1-76) UBC(305-380) GTF2H5 RFC1 SUMO3 MNAT1 Ub,p-S2,S5-POLR2A POLE4 RBX1 GTF2H1 UBC(381-456) UBC(1-76) UBC(305-380) PARP2 Ub-63-UBC(1-76) HMGN1 ERCC2 SUMO1,2,3:UBE2IPAR-PARP2 POLR2E ERCC8:DDB1:CUL4:RBX1UBE2V2 RAD23B GTF2H5 POLR2H UBC(77-152) GTF2H2 Distorted dsDNAUBB(1-76) EP300RAD23B UBB(77-152) GTF2H5 ERCC5 POLD1 UBC(229-304) Ub,p-S2,S5-POLR2A GTF2H3 Ub,p-S2,S5-POLR2A ERCC6 PCNA ERCC3 Ub-139-UBB(77-152) PPIE UBB(153-228) GTF2H3 POLE4 POLD4 UBC(381-456) POLR2B UBC(229-304) RFC3 UBB(1-76) UBB(1-76) UBB(1-76) CUL4A CDK7 Distorted dsDNA COPS7A ERCC6CHD1L CUL4B POLR2C Ub,SUMO-XPC Ub:XPC:RAD23:CETN2:Distorted dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1,PAR-PARP2:CHD1LDDB1 POLR2E UBC(533-608) UBC(229-304) UBC(1-76) UBC(305-380) PCNAhomotrimer,MonoUb:K164-PCNA homotrimerPOLD3 ERCC2 Ub,SUMO,K63polyUb-XPC AQR CCNH UVSSA POLR2I RFC4 PARP1 UVSSA UBC(153-228) GTF2H2 UBB(77-152) UBA52(1-76) ERCC4 RAD23B GTF2H4 UBC(609-684) UBC(77-152) UBC(1-76) POLK GTF2H1 UBC(77-152) POLD2 AQR UBB(153-228) RPA2 GPS1 POLR2G POLR2F UBC(77-152) UBA52(1-76) ERCC2 USP7 GG-NER pre-incisioncomplex:Openbubble-dsDNASUMO3-C93-UBE2I RAD23A RAD23A UBB(77-152) UBB(1-76) UBC(609-684) UBC(381-456) UBC(609-684) XPA MNAT1 COPS5 UBB(1-76) ERCC5 POLR2I RAD23A damaged DNA with 5' incision UBC(153-228) POLR2J POLR2F POLR2B HyperphosphorylatedRNA Pol II:DamagedDNAtemplate:nascentmRNA hybrid:TFIIHPOLR2L CDK7 excised DNA fragmentwith lesionRFC4 UBC(153-228) RPA1 CUL4B POLR2G UBC(77-152) POLR2I UBA52(1-76) DDB2 Ub-XPC POLR2B POLR2G UBA52(1-76) Ub-367-UBC(305-380) RFC2 DDB1 Ub-139-UBB(77-152) PIAS1 UBA52(1-76) PAR-PARP1 Distorted dsDNA COPS4 UBA52(1-76) POLR2K Ub:XPC:RAD23:CETN2:Distorted dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1,PAR-PARP2ISY1 POLD4 POLR2J POLR2D UVSSA UBA52(1-76) XPA GTF2H3 COPS3 TCEA1 UBC(77-152) USP7 CUL4A CCNH UBC(153-228) UBC(381-456) MonoUb-K164-PCNA UBB(153-228) POLR2B POLR2E POLE3 UBB(153-228) Ub-291-UBC(229-304) ZNF830 UBC(533-608) POLR2I DDB1 POLR2K UBB(153-228) UBB(77-152) POLR2C UbUBC(153-228) GTF2H2 RFC1 POLE2 ERCC8 Openbubble-dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1, PAR-PARP2:CHD1LPOLK UBC(533-608) DDB1 XAB2 ACTB(1-375) UBC(609-684) UBB(153-228) CUL4B AQR TCEA1 ERCC4 RAD23A GTF2H4 DDB1 PRPF19 CDK7 ACTR5 UBC(457-532) Ub-215-UBB(153-228) HMGN1 GTF2H4 MonoUb-K164-PCNA RPS27A(1-76) GTF2H1 TC-NER pre-incisioncomplex:Open bubbledamaged DNAtemplate:trimmednascent mRNAUBE2N POLR2H UBC(77-152) DDB1 MNAT1 XPC:RAD23:CETN2:Distorted dsDNA:UV-DDBUBB(153-228) CCNH UBC(609-684) UBC(153-228) POLR2G RFC2 TC-NER post-incisioncomplex:dsDNA withtranscriptionbubbleUb-139-UBC(77-152) UBE2IdNTPSUMO1 RAD23B UBC(305-380) ACTL6A POLR2K RBX1 MNAT1 ERCC2 UBC(381-456) GTF2H4 UBB(77-152) 5576, 9955599555576, 9955583555551005514, 54, 875511, 14, 54, 875100551005553555533555599589789555555576, 995559955555551005555510055555355


Description

Nucleotide excision repair (NER) was first described in the model organism E. coli in the early 1960s as a process whereby bulky base damage is enzymatically removed from DNA, facilitating the recovery of DNA synthesis and cell survival. Deficient NER processes have been identified from the cells of cancer-prone patients with different variants of xeroderma pigmentosum (XP), trichothiodystrophy (TTD), and Cockayne's syndrome. The XP cells exhibit an ultraviolet radiation hypersensitivity that leads to a hypermutability response to UV, offering a direct connection between deficient NER, increased mutation rate, and cancer. While the NER pathway in prokaryotes is unique, the pathway utilized in yeast and higher eukaryotes is highly conserved.
NER is involved in the repair of bulky adducts in DNA, such as UV-induced photo lesions (both 6-4 photoproducts (6-4 PPDs) and cyclobutane pyrimidine dimers (CPDs)), as well as chemical adducts formed from exposure to aflatoxin, benzopyrene and other genotoxic agents. Specific proteins have been identified that participate in base damage recognition, cleavage of the damaged strand on both sides of the lesion, and excision of the oligonucleotide bearing the lesion. Reparative DNA synthesis and ligation restore the strand to its original state.
NER consists of two related pathways called global genome nucleotide excision repair (GG-NER) and transcription-coupled nucleotide excision repair (TC-NER). The pathways differ in the way in which DNA damage is initially recognized, but the majority of the participating molecules are shared between these two branches of NER. GG-NER is transcription-independent, removing lesions from non-coding DNA strands, as well as coding DNA strands that are not being actively transcribed. TC-NER repairs damage in transcribed strands of active genes.
Several of the proteins involved in NER are key components of the basal transcription complex TFIIH. An ubiquitin ligase complex composed of DDB1, CUL4A or CUL4B and RBX1 participates in both GG-NER and TC-NER, implying an important role of ubiquitination in NER regulation. The establishment of mutant mouse models for NER genes and other DNA repair-related genes has been useful in demonstrating the associations between NER defects and cancer.
For past and recent reviews of nucleotide excision repair, please refer to Lindahl and Wood 1998, Friedberg et al. 2002, Christmann et al. 2003, Hanawalt and Spivak 2008, Marteijn et al. 2014). View original pathway at Reactome.

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Reactome-Converter 
Pathway is converted from Reactome ID: 5696398
Reactome-version 
Reactome version: 75
Reactome Author 
Reactome Author: Hoeijmakers, Jan H J

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Bibliography

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  1. Wang QE, Zhu Q, Wani G, Chen J, Wani AA.; ''UV radiation-induced XPC translocation within chromatin is mediated by damaged-DNA binding protein, DDB2.''; PubMed Europe PMC Scholia
  2. Robu M, Shah RG, Petitclerc N, Brind'Amour J, Kandan-Kulangara F, Shah GM.; ''Role of poly(ADP-ribose) polymerase-1 in the removal of UV-induced DNA lesions by nucleotide excision repair.''; PubMed Europe PMC Scholia
  3. Fousteri M, Vermeulen W, van Zeeland AA, Mullenders LH.; ''Cockayne syndrome A and B proteins differentially regulate recruitment of chromatin remodeling and repair factors to stalled RNA polymerase II in vivo.''; PubMed Europe PMC Scholia
  4. Lee KB, Wang D, Lippard SJ, Sharp PA.; ''Transcription-coupled and DNA damage-dependent ubiquitination of RNA polymerase II in vitro.''; PubMed Europe PMC Scholia
  5. Shiyanov P, Nag A, Raychaudhuri P.; ''Cullin 4A associates with the UV-damaged DNA-binding protein DDB.''; PubMed Europe PMC Scholia
  6. Masutani C, Sugasawa K, Yanagisawa J, Sonoyama T, Ui M, Enomoto T, Takio K, Tanaka K, van der Spek PJ, Bootsma D.; ''Purification and cloning of a nucleotide excision repair complex involving the xeroderma pigmentosum group C protein and a human homologue of yeast RAD23.''; PubMed Europe PMC Scholia
  7. Winkler GS, Sugasawa K, Eker AP, de Laat WL, Hoeijmakers JH.; ''Novel functional interactions between nucleotide excision DNA repair proteins influencing the enzymatic activities of TFIIH, XPG, and ERCC1-XPF.''; PubMed Europe PMC Scholia
  8. Wang H, Zhai L, Xu J, Joo HY, Jackson S, Erdjument-Bromage H, Tempst P, Xiong Y, Zhang Y.; ''Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage.''; PubMed Europe PMC Scholia
  9. Ito S, Kuraoka I, Chymkowitch P, Compe E, Takedachi A, Ishigami C, Coin F, Egly JM, Tanaka K.; ''XPG stabilizes TFIIH, allowing transactivation of nuclear receptors: implications for Cockayne syndrome in XP-G/CS patients.''; PubMed Europe PMC Scholia
  10. Birger Y, West KL, Postnikov YV, Lim JH, Furusawa T, Wagner JP, Laufer CS, Kraemer KH, Bustin M.; ''Chromosomal protein HMGN1 enhances the rate of DNA repair in chromatin.''; PubMed Europe PMC Scholia
  11. Coin F, Oksenych V, Mocquet V, Groh S, Blattner C, Egly JM.; ''Nucleotide excision repair driven by the dissociation of CAK from TFIIH.''; PubMed Europe PMC Scholia
  12. Brueckner F, Hennecke U, Carell T, Cramer P.; ''CPD damage recognition by transcribing RNA polymerase II.''; PubMed Europe PMC Scholia
  13. Ziani S, Nagy Z, Alekseev S, Soutoglou E, Egly JM, Coin F.; ''Sequential and ordered assembly of a large DNA repair complex on undamaged chromatin.''; PubMed Europe PMC Scholia
  14. Schultz P, Fribourg S, Poterszman A, Mallouh V, Moras D, Egly JM.; ''Molecular structure of human TFIIH.''; PubMed Europe PMC Scholia
  15. Bregman DB, Halaban R, van Gool AJ, Henning KA, Friedberg EC, Warren SL.; ''UV-induced ubiquitination of RNA polymerase II: a novel modification deficient in Cockayne syndrome cells.''; PubMed Europe PMC Scholia
  16. Furuta T, Ueda T, Aune G, Sarasin A, Kraemer KH, Pommier Y.; ''Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cells.''; PubMed Europe PMC Scholia
  17. Friedberg EC.; ''How nucleotide excision repair protects against cancer.''; PubMed Europe PMC Scholia
  18. Orelli B, McClendon TB, Tsodikov OV, Ellenberger T, Niedernhofer LJ, Schärer OD.; ''The XPA-binding domain of ERCC1 is required for nucleotide excision repair but not other DNA repair pathways.''; PubMed Europe PMC Scholia
  19. Selby CP, Sancar A.; ''Cockayne syndrome group B protein enhances elongation by RNA polymerase II.''; PubMed Europe PMC Scholia
  20. Kuper J, Wolski SC, Michels G, Kisker C.; ''Functional and structural studies of the nucleotide excision repair helicase XPD suggest a polarity for DNA translocation.''; PubMed Europe PMC Scholia
  21. Yokoi M, Masutani C, Maekawa T, Sugasawa K, Ohkuma Y, Hanaoka F.; ''The xeroderma pigmentosum group C protein complex XPC-HR23B plays an important role in the recruitment of transcription factor IIH to damaged DNA.''; PubMed Europe PMC Scholia
  22. Fujiwara Y, Masutani C, Mizukoshi T, Kondo J, Hanaoka F, Iwai S.; ''Characterization of DNA recognition by the human UV-damaged DNA-binding protein.''; PubMed Europe PMC Scholia
  23. Ng JM, Vermeulen W, van der Horst GT, Bergink S, Sugasawa K, Vrieling H, Hoeijmakers JH.; ''A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein.''; PubMed Europe PMC Scholia
  24. Camenisch U, Dip R, Schumacher SB, Schuler B, Naegeli H.; ''Recognition of helical kinks by xeroderma pigmentosum group A protein triggers DNA excision repair.''; PubMed Europe PMC Scholia
  25. Pines A, Vrouwe MG, Marteijn JA, Typas D, Luijsterburg MS, Cansoy M, Hensbergen P, Deelder A, de Groot A, Matsumoto S, Sugasawa K, Thoma N, Vermeulen W, Vrieling H, Mullenders L.; ''PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1.''; PubMed Europe PMC Scholia
  26. Anindya R, Mari PO, Kristensen U, Kool H, Giglia-Mari G, Giglia-Mari G, Mullenders LH, Fousteri M, Vermeulen W, Egly JM, Svejstrup JQ.; ''A ubiquitin-binding domain in Cockayne syndrome B required for transcription-coupled nucleotide excision repair.''; PubMed Europe PMC Scholia
  27. Overmeer RM, Moser J, Volker M, Kool H, Tomkinson AE, van Zeeland AA, Mullenders LH, Fousteri M.; ''Replication protein A safeguards genome integrity by controlling NER incision events.''; PubMed Europe PMC Scholia
  28. Dunand-Sauthier I, Hohl M, Thorel F, Jaquier-Gubler P, Clarkson SG, Schärer OD.; ''The spacer region of XPG mediates recruitment to nucleotide excision repair complexes and determines substrate specificity.''; PubMed Europe PMC Scholia
  29. King BS, Cooper KL, Liu KJ, Hudson LG.; ''Poly(ADP-ribose) contributes to an association between poly(ADP-ribose) polymerase-1 and xeroderma pigmentosum complementation group A in nucleotide excision repair.''; PubMed Europe PMC Scholia
  30. Park CH, Bessho T, Matsunaga T, Sancar A.; ''Purification and characterization of the XPF-ERCC1 complex of human DNA repair excision nuclease.''; PubMed Europe PMC Scholia
  31. Nakatsu Y, Asahina H, Citterio E, Rademakers S, Vermeulen W, Kamiuchi S, Yeo JP, Khaw MC, Saijo M, Kodo N, Matsuda T, Hoeijmakers JH, Tanaka K.; ''XAB2, a novel tetratricopeptide repeat protein involved in transcription-coupled DNA repair and transcription.''; PubMed Europe PMC Scholia
  32. Dinant C, Ampatziadis-Michailidis G, Lans H, Tresini M, Lagarou A, Grosbart M, Theil AF, van Cappellen WA, Kimura H, Bartek J, Fousteri M, Houtsmuller AB, Vermeulen W, Marteijn JA.; ''Enhanced chromatin dynamics by FACT promotes transcriptional restart after UV-induced DNA damage.''; PubMed Europe PMC Scholia
  33. Conaway RC, Conaway JW.; ''The INO80 chromatin remodeling complex in transcription, replication and repair.''; PubMed Europe PMC Scholia
  34. Mackinnon-Roy C, Stubbert LJ, McKay BC.; ''RNA interference against transcription elongation factor SII does not support its role in transcription-coupled nucleotide excision repair.''; PubMed Europe PMC Scholia
  35. Riedl T, Hanaoka F, Egly JM.; ''The comings and goings of nucleotide excision repair factors on damaged DNA.''; PubMed Europe PMC Scholia
  36. Ikegami T, Kuraoka I, Saijo M, Kodo N, Kyogoku Y, Morikawa K, Tanaka K, Shirakawa M.; ''Solution structure of the DNA- and RPA-binding domain of the human repair factor XPA.''; PubMed Europe PMC Scholia
  37. Christmann M, Tomicic MT, Roos WP, Kaina B.; ''Mechanisms of human DNA repair: an update.''; PubMed Europe PMC Scholia
  38. Min JH, Pavletich NP.; ''Recognition of DNA damage by the Rad4 nucleotide excision repair protein.''; PubMed Europe PMC Scholia
  39. Schwertman P, Lagarou A, Dekkers DH, Raams A, van der Hoek AC, Laffeber C, Hoeijmakers JH, Demmers JA, Fousteri M, Vermeulen W, Marteijn JA.; ''UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair.''; PubMed Europe PMC Scholia
  40. Marteijn JA, Lans H, Vermeulen W, Hoeijmakers JH.; ''Understanding nucleotide excision repair and its roles in cancer and ageing.''; PubMed Europe PMC Scholia
  41. Araki M, Masutani C, Takemura M, Uchida A, Sugasawa K, Kondoh J, Ohkuma Y, Hanaoka F.; ''Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair.''; PubMed Europe PMC Scholia
  42. Sollier J, Stork CT, García-Rubio ML, Paulsen RD, Aguilera A, Cimprich KA.; ''Transcription-coupled nucleotide excision repair factors promote R-loop-induced genome instability.''; PubMed Europe PMC Scholia
  43. Mourgues S, Gautier V, Lagarou A, Bordier C, Mourcet A, Slingerland J, Kaddoum L, Coin F, Vermeulen W, Gonzales de Peredo A, Monsarrat B, Mari PO, Giglia-Mari G.; ''ELL, a novel TFIIH partner, is involved in transcription restart after DNA repair.''; PubMed Europe PMC Scholia
  44. Wang QE, Zhu Q, Wani G, El-Mahdy MA, Li J, Wani AA.; ''DNA repair factor XPC is modified by SUMO-1 and ubiquitin following UV irradiation.''; PubMed Europe PMC Scholia
  45. Balajee AS, May A, Dianova I, Bohr VA.; ''Efficient PCNA complex formation is dependent upon both transcription coupled repair and genome overall repair.''; PubMed Europe PMC Scholia
  46. Scrima A, Konícková R, Czyzewski BK, Kawasaki Y, Jeffrey PD, Groisman R, Groisman R, Nakatani Y, Iwai S, Pavletich NP, Thomä NH.; ''Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex.''; PubMed Europe PMC Scholia
  47. Hanawalt PC, Spivak G.; ''Transcription-coupled DNA repair: two decades of progress and surprises.''; PubMed Europe PMC Scholia
  48. Jiang Y, Wang X, Bao S, Guo R, Johnson DG, Shen X, Li L.; ''INO80 chromatin remodeling complex promotes the removal of UV lesions by the nucleotide excision repair pathway.''; PubMed Europe PMC Scholia
  49. Wakasugi M, Shimizu M, Morioka H, Linn S, Nikaido O, Matsunaga T.; ''Damaged DNA-binding protein DDB stimulates the excision of cyclobutane pyrimidine dimers in vitro in concert with XPA and replication protein A.''; PubMed Europe PMC Scholia
  50. Fei J, Chen J.; ''KIAA1530 protein is recruited by Cockayne syndrome complementation group protein A (CSA) to participate in transcription-coupled repair (TCR).''; PubMed Europe PMC Scholia
  51. Sugasawa K, Akagi J, Nishi R, Iwai S, Hanaoka F.; ''Two-step recognition of DNA damage for mammalian nucleotide excision repair: Directional binding of the XPC complex and DNA strand scanning.''; PubMed Europe PMC Scholia
  52. Tsodikov OV, Ivanov D, Orelli B, Staresincic L, Shoshani I, Oberman R, Schärer OD, Wagner G, Ellenberger T.; ''Structural basis for the recruitment of ERCC1-XPF to nucleotide excision repair complexes by XPA.''; PubMed Europe PMC Scholia
  53. Sarker AH, Tsutakawa SE, Kostek S, Ng C, Shin DS, Peris M, Campeau E, Tainer JA, Nogales E, Cooper PK.; ''Recognition of RNA polymerase II and transcription bubbles by XPG, CSB, and TFIIH: insights for transcription-coupled repair and Cockayne Syndrome.''; PubMed Europe PMC Scholia
  54. Rossignol M, Kolb-Cheynel I, Egly JM.; ''Substrate specificity of the cdk-activating kinase (CAK) is altered upon association with TFIIH.''; PubMed Europe PMC Scholia
  55. Mathieu N, Kaczmarek N, Naegeli H.; ''Strand- and site-specific DNA lesion demarcation by the xeroderma pigmentosum group D helicase.''; PubMed Europe PMC Scholia
  56. Zhang X, Horibata K, Saijo M, Ishigami C, Ukai A, Kanno S, Tahara H, Neilan EG, Honma M, Nohmi T, Yasui A, Tanaka K.; ''Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in transcription-coupled DNA repair.''; PubMed Europe PMC Scholia
  57. Poulsen SL, Hansen RK, Wagner SA, van Cuijk L, van Belle GJ, Streicher W, Wikström M, Choudhary C, Houtsmuller AB, Marteijn JA, Bekker-Jensen S, Mailand N.; ''RNF111/Arkadia is a SUMO-targeted ubiquitin ligase that facilitates the DNA damage response.''; PubMed Europe PMC Scholia
  58. Fang L, Wang X, Yamoah K, Chen PL, Pan ZQ, Huang L.; ''Characterization of the human COP9 signalosome complex using affinity purification and mass spectrometry.''; PubMed Europe PMC Scholia
  59. Jawhari A, Lainé JP, Dubaele S, Lamour V, Poterszman A, Coin F, Moras D, Egly JM.; ''p52 Mediates XPB function within the transcription/repair factor TFIIH.''; PubMed Europe PMC Scholia
  60. Epshtein V, Kamarthapu V, McGary K, Svetlov V, Ueberheide B, Proshkin S, Mironov A, Nudler E.; ''UvrD facilitates DNA repair by pulling RNA polymerase backwards.''; PubMed Europe PMC Scholia
  61. Moser J, Kool H, Giakzidis I, Caldecott K, Mullenders LH, Fousteri MI.; ''Sealing of chromosomal DNA nicks during nucleotide excision repair requires XRCC1 and DNA ligase III alpha in a cell-cycle-specific manner.''; PubMed Europe PMC Scholia
  62. Akita M, Tak YS, Shimura T, Matsumoto S, Okuda-Shimizu Y, Shimizu Y, Nishi R, Saitoh H, Iwai S, Mori T, Ikura T, Sakai W, Hanaoka F, Sugasawa K.; ''SUMOylation of xeroderma pigmentosum group C protein regulates DNA damage recognition during nucleotide excision repair.''; PubMed Europe PMC Scholia
  63. Oksenych V, Bernardes de Jesus B, Zhovmer A, Egly JM, Coin F.; ''Molecular insights into the recruitment of TFIIH to sites of DNA damage.''; PubMed Europe PMC Scholia
  64. Ahel D, Horejsí Z, Wiechens N, Polo SE, Garcia-Wilson E, Ahel I, Flynn H, Skehel M, West SC, Jackson SP, Owen-Hughes T, Boulton SJ.; ''Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1.''; PubMed Europe PMC Scholia
  65. Coin F, Marinoni JC, Rodolfo C, Fribourg S, Pedrini AM, Egly JM.; ''Mutations in the XPD helicase gene result in XP and TTD phenotypes, preventing interaction between XPD and the p44 subunit of TFIIH.''; PubMed Europe PMC Scholia
  66. Reardon JT, Ge H, Gibbs E, Sancar A, Hurwitz J, Pan ZQ.; ''Isolation and characterization of two human transcription factor IIH (TFIIH)-related complexes: ERCC2/CAK and TFIIH.''; PubMed Europe PMC Scholia
  67. Groisman R, Groisman R, Kuraoka I, Chevallier O, Gaye N, Magnaldo T, Tanaka K, Kisselev AF, Harel-Bellan A, Nakatani Y.; ''CSA-dependent degradation of CSB by the ubiquitin-proteasome pathway establishes a link between complementation factors of the Cockayne syndrome.''; PubMed Europe PMC Scholia
  68. Vermeulen W, Fousteri M.; ''Mammalian transcription-coupled excision repair.''; PubMed Europe PMC Scholia
  69. Ogi T, Limsirichaikul S, Overmeer RM, Volker M, Takenaka K, Cloney R, Nakazawa Y, Niimi A, Miki Y, Jaspers NG, Mullenders LH, Yamashita S, Fousteri MI, Lehmann AR.; ''Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells.''; PubMed Europe PMC Scholia
  70. Donahue BA, Yin S, Taylor JS, Reines D, Hanawalt PC.; ''Transcript cleavage by RNA polymerase II arrested by a cyclobutane pyrimidine dimer in the DNA template.''; PubMed Europe PMC Scholia
  71. Groisman R, Groisman R, Polanowska J, Kuraoka I, Sawada J, Saijo M, Drapkin R, Kisselev AF, Tanaka K, Nakatani Y.; ''The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage.''; PubMed Europe PMC Scholia
  72. Moser J, Volker M, Kool H, Alekseev S, Vrieling H, Yasui A, van Zeeland AA, Mullenders LH.; ''The UV-damaged DNA binding protein mediates efficient targeting of the nucleotide excision repair complex to UV-induced photo lesions.''; PubMed Europe PMC Scholia
  73. Zotter A, Luijsterburg MS, Warmerdam DO, Ibrahim S, Nigg A, van Cappellen WA, Hoeijmakers JH, van Driel R, Vermeulen W, Houtsmuller AB.; ''Recruitment of the nucleotide excision repair endonuclease XPG to sites of UV-induced dna damage depends on functional TFIIH.''; PubMed Europe PMC Scholia
  74. Nishi R, Okuda Y, Watanabe E, Mori T, Iwai S, Masutani C, Sugasawa K, Hanaoka F.; ''Centrin 2 stimulates nucleotide excision repair by interacting with xeroderma pigmentosum group C protein.''; PubMed Europe PMC Scholia
  75. Perez-Oliva AB, Lachaud C, Szyniarowski P, Muñoz I, Macartney T, Hickson I, Rouse J, Alessi DR.; ''USP45 deubiquitylase controls ERCC1-XPF endonuclease-mediated DNA damage responses.''; PubMed Europe PMC Scholia
  76. Kamitani T, Kito K, Nguyen HP, Fukuda-Kamitani T, Yeh ET.; ''Characterization of a second member of the sentrin family of ubiquitin-like proteins.''; PubMed Europe PMC Scholia
  77. Nakazawa Y, Sasaki K, Mitsutake N, Matsuse M, Shimada M, Nardo T, Takahashi Y, Ohyama K, Ito K, Mishima H, Nomura M, Kinoshita A, Ono S, Takenaka K, Masuyama R, Kudo T, Slor H, Utani A, Tateishi S, Yamashita S, Stefanini M, Lehmann AR, Yoshiura K, Ogi T.; ''Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair.''; PubMed Europe PMC Scholia
  78. Wittschieben BØ, Iwai S, Wood RD.; ''DDB1-DDB2 (xeroderma pigmentosum group E) protein complex recognizes a cyclobutane pyrimidine dimer, mismatches, apurinic/apyrimidinic sites, and compound lesions in DNA.''; PubMed Europe PMC Scholia
  79. Wakasugi M, Kasashima H, Fukase Y, Imura M, Imai R, Yamada S, Cleaver JE, Matsunaga T.; ''Physical and functional interaction between DDB and XPA in nucleotide excision repair.''; PubMed Europe PMC Scholia
  80. He Z, Henricksen LA, Wold MS, Ingles CJ.; ''RPA involvement in the damage-recognition and incision steps of nucleotide excision repair.''; PubMed Europe PMC Scholia
  81. Volker M, Moné MJ, Karmakar P, van Hoffen A, Schul W, Vermeulen W, Hoeijmakers JH, van Driel R, van Zeeland AA, Mullenders LH.; ''Sequential assembly of the nucleotide excision repair factors in vivo.''; PubMed Europe PMC Scholia
  82. Kapetanaki MG, Guerrero-Santoro J, Bisi DC, Hsieh CL, Rapić-Otrin V, Levine AS.; ''The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites.''; PubMed Europe PMC Scholia
  83. Hofmann RM, Pickart CM.; ''Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair.''; PubMed Europe PMC Scholia
  84. Sarkar S, Kiely R, McHugh PJ.; ''The Ino80 chromatin-remodeling complex restores chromatin structure during UV DNA damage repair.''; PubMed Europe PMC Scholia
  85. Mocquet V, Lainé JP, Riedl T, Yajin Z, Lee MY, Egly JM.; ''Sequential recruitment of the repair factors during NER: the role of XPG in initiating the resynthesis step.''; PubMed Europe PMC Scholia
  86. Mathieu N, Kaczmarek N, Rüthemann P, Luch A, Naegeli H.; ''DNA quality control by a lesion sensor pocket of the xeroderma pigmentosum group D helicase subunit of TFIIH.''; PubMed Europe PMC Scholia
  87. Giglia-Mari G, Giglia-Mari G, Coin F, Ranish JA, Hoogstraten D, Theil A, Wijgers N, Jaspers NG, Raams A, Argentini M, van der Spek PJ, Botta E, Stefanini M, Egly JM, Aebersold R, Hoeijmakers JH, Vermeulen W.; ''A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A.''; PubMed Europe PMC Scholia
  88. Fischer ES, Scrima A, Böhm K, Matsumoto S, Lingaraju GM, Faty M, Yasuda T, Cavadini S, Wakasugi M, Hanaoka F, Iwai S, Gut H, Sugasawa K, Thomä NH.; ''The molecular basis of CRL4DDB2/CSA ubiquitin ligase architecture, targeting, and activation.''; PubMed Europe PMC Scholia
  89. Staresincic L, Fagbemi AF, Enzlin JH, Gourdin AM, Wijgers N, Dunand-Sauthier I, Giglia-Mari G, Giglia-Mari G, Clarkson SG, Vermeulen W, Schärer OD.; ''Coordination of dual incision and repair synthesis in human nucleotide excision repair.''; PubMed Europe PMC Scholia
  90. Camenisch U, Träutlein D, Clement FC, Fei J, Leitenstorfer A, Ferrando-May E, Naegeli H.; ''Two-stage dynamic DNA quality check by xeroderma pigmentosum group C protein.''; PubMed Europe PMC Scholia
  91. de Laat WL, Appeldoorn E, Sugasawa K, Weterings E, Jaspers NG, Hoeijmakers JH.; ''DNA-binding polarity of human replication protein A positions nucleases in nucleotide excision repair.''; PubMed Europe PMC Scholia
  92. Takedachi A, Saijo M, Tanaka K.; ''DDB2 complex-mediated ubiquitylation around DNA damage is oppositely regulated by XPC and Ku and contributes to the recruitment of XPA.''; PubMed Europe PMC Scholia
  93. Fitch ME, Nakajima S, Yasui A, Ford JM.; ''In vivo recruitment of XPC to UV-induced cyclobutane pyrimidine dimers by the DDB2 gene product.''; PubMed Europe PMC Scholia
  94. Sugasawa K, Okuda Y, Saijo M, Nishi R, Matsuda N, Chu G, Mori T, Iwai S, Tanaka K, Tanaka K, Hanaoka F.; ''UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex.''; PubMed Europe PMC Scholia
  95. Coin F, Oksenych V, Egly JM.; ''Distinct roles for the XPB/p52 and XPD/p44 subcomplexes of TFIIH in damaged DNA opening during nucleotide excision repair.''; PubMed Europe PMC Scholia
  96. Oh KS, Imoto K, Emmert S, Tamura D, DiGiovanna JJ, Kraemer KH.; ''Nucleotide excision repair proteins rapidly accumulate but fail to persist in human XP-E (DDB2 mutant) cells.''; PubMed Europe PMC Scholia
  97. Kuraoka I, Ito S, Wada T, Hayashida M, Lee L, Saijo M, Nakatsu Y, Matsumoto M, Matsunaga T, Handa H, Qin J, Nakatani Y, Tanaka K.; ''Isolation of XAB2 complex involved in pre-mRNA splicing, transcription, and transcription-coupled repair.''; PubMed Europe PMC Scholia
  98. van Cuijk L, van Belle GJ, van Belle GJ, Turkyilmaz Y, Poulsen SL, Janssens RC, Theil AF, Sabatella M, Lans H, Mailand N, Houtsmuller AB, Vermeulen W, Marteijn JA.; ''SUMO and ubiquitin-dependent XPC exchange drives nucleotide excision repair.''; PubMed Europe PMC Scholia
  99. Su HL, Li SS.; ''Molecular features of human ubiquitin-like SUMO genes and their encoded proteins.''; PubMed Europe PMC Scholia
  100. Morris DP, Michelotti GA, Schwinn DA.; ''Evidence that phosphorylation of the RNA polymerase II carboxyl-terminal repeats is similar in yeast and humans.''; PubMed Europe PMC Scholia
  101. Lindahl T, Wood RD.; ''Quality control by DNA repair.''; PubMed Europe PMC Scholia
  102. Araújo SJ, Wood RD.; ''Protein complexes in nucleotide excision repair.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
115027view16:56, 25 January 2021ReactomeTeamReactome version 75
113472view11:54, 2 November 2020ReactomeTeamReactome version 74
112671view16:06, 9 October 2020ReactomeTeamReactome version 73
101588view11:45, 1 November 2018ReactomeTeamreactome version 66
101124view21:29, 31 October 2018ReactomeTeamreactome version 65
100652view20:03, 31 October 2018ReactomeTeamreactome version 64
100202view16:48, 31 October 2018ReactomeTeamreactome version 63
99753view15:14, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93777view13:35, 16 August 2017ReactomeTeamreactome version 61
93305view11:19, 9 August 2017ReactomeTeamreactome version 61
88077view09:04, 26 July 2016RyanmillerOntology Term : 'DNA repair pathway' added !
88076view09:02, 26 July 2016RyanmillerOntology Term : 'regulatory pathway' added !
86389view09:16, 11 July 2016ReactomeTeamreactome version 56
83072view09:53, 18 November 2015ReactomeTeamVersion54
81391view12:55, 21 August 2015ReactomeTeamVersion53
76859view08:13, 17 July 2014ReactomeTeamFixed remaining interactions
76564view11:54, 16 July 2014ReactomeTeamFixed remaining interactions
75897view09:55, 11 June 2014ReactomeTeamRe-fixing comment source
75597view10:44, 10 June 2014ReactomeTeamReactome 48 Update
74952view13:47, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74596view08:38, 30 April 2014ReactomeTeamReactome46
42219view00:30, 8 March 2011MaintBotModified categories
42218view00:23, 8 March 2011MaintBot
42217view00:22, 8 March 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
(PCNA:POLD,POLE), (MonoUb:K164-PCNA:POLK):RPA:RFC:Incised DNA without lesionComplexR-HSA-5690478 (Reactome)
(PCNA:POLD,POLE), (MonoUb:K164-PCNA:POLK):RPA:RFC:SSB-dsDNAComplexR-HSA-5690470 (Reactome)
(PCNA:POLD,POLE), (MonoUb:K164-PCNA:POLK):RPA:RFCComplexR-HSA-6790530 (Reactome)
5'-incised damaged DNA:trimmed nascent mRNA R-ALL-6782202 (Reactome)
ACTB(1-375) ProteinP60709 (Uniprot-TrEMBL)
ACTL6A ProteinO96019 (Uniprot-TrEMBL)
ACTR5 ProteinQ9H9F9 (Uniprot-TrEMBL)
ACTR8 ProteinQ9H981 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:456216 (ChEBI)
AQR ProteinO60306 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:30616 (ChEBI)
CAKComplexR-HSA-69221 (Reactome)
CCNH ProteinP51946 (Uniprot-TrEMBL)
CDK7 ProteinP50613 (Uniprot-TrEMBL)
CETN2 ProteinP41208 (Uniprot-TrEMBL)
CETN2ProteinP41208 (Uniprot-TrEMBL)
CHD1L ProteinQ86WJ1 (Uniprot-TrEMBL)
CHD1LProteinQ86WJ1 (Uniprot-TrEMBL)
COP9 signalosomeComplexR-HSA-5697024 (Reactome)
COPS2 ProteinP61201 (Uniprot-TrEMBL)
COPS3 ProteinQ9UNS2 (Uniprot-TrEMBL)
COPS4 ProteinQ9BT78 (Uniprot-TrEMBL)
COPS5 ProteinQ92905 (Uniprot-TrEMBL)
COPS6 ProteinQ7L5N1 (Uniprot-TrEMBL)
COPS7A ProteinQ9UBW8 (Uniprot-TrEMBL)
COPS7B ProteinQ9H9Q2 (Uniprot-TrEMBL)
COPS8 ProteinQ99627 (Uniprot-TrEMBL)
CUL4A ProteinQ13619 (Uniprot-TrEMBL)
CUL4B ProteinQ13620 (Uniprot-TrEMBL)
DDB1 ProteinQ16531 (Uniprot-TrEMBL)
DDB2 ProteinQ92466 (Uniprot-TrEMBL)
Damaged

dsDNA with open transcription

bubble:Hyperphosphorylated RNA Pol II:TFIIH
ComplexR-HSA-6781821 (Reactome)
Damaged dsDNA with open transcription bubble R-ALL-6781820 (Reactome)
Distorted dsDNA R-ALL-5688114 (Reactome)
Distorted dsDNAR-ALL-5688114 (Reactome)
ELLProteinP55199 (Uniprot-TrEMBL)
EP300 ProteinQ09472 (Uniprot-TrEMBL)
EP300ProteinQ09472 (Uniprot-TrEMBL)
ERCC1 ProteinP07992 (Uniprot-TrEMBL)
ERCC1:ERCC4ComplexR-HSA-109943 (Reactome)
ERCC1ProteinP07992 (Uniprot-TrEMBL)
ERCC2 ProteinP18074 (Uniprot-TrEMBL)
ERCC3 ProteinP19447 (Uniprot-TrEMBL)
ERCC4 ProteinQ92889 (Uniprot-TrEMBL)
ERCC4ProteinQ92889 (Uniprot-TrEMBL)
ERCC5 ProteinP28715 (Uniprot-TrEMBL)
ERCC5ProteinP28715 (Uniprot-TrEMBL)
ERCC6 ProteinQ03468 (Uniprot-TrEMBL)
ERCC6ProteinQ03468 (Uniprot-TrEMBL)
ERCC8 ProteinQ13216 (Uniprot-TrEMBL)
ERCC8:DDB1:CUL4:RBX1:COP9 SignalosomeComplexR-HSA-6781842 (Reactome)
ERCC8:DDB1:CUL4:RBX1ComplexR-HSA-6781841 (Reactome)
GG-NER

incision complex:5'-incised damaged

DNA:(PCNA:POLD,POLE),(MonoUb:K164-PCNA:POLK):RPA:RFC
ComplexR-HSA-5690214 (Reactome)
GG-NER incision

complex:5'-incised

damaged DNA
ComplexR-HSA-5691059 (Reactome)
GG-NER incision

complex:Open bubble

dsDNA
ComplexR-HSA-5691046 (Reactome)
GG-NER pre-incision

complex:Open

bubble-dsDNA
ComplexR-HSA-5691043 (Reactome)
GPS1 ProteinQ13098 (Uniprot-TrEMBL)
GTF2H1 ProteinP32780 (Uniprot-TrEMBL)
GTF2H2 ProteinQ13888 (Uniprot-TrEMBL)
GTF2H3 ProteinQ13889 (Uniprot-TrEMBL)
GTF2H4 ProteinQ92759 (Uniprot-TrEMBL)
GTF2H5 ProteinQ6ZYL4 (Uniprot-TrEMBL)
H2OMetaboliteCHEBI:15377 (ChEBI)
HMGN1 ProteinP05114 (Uniprot-TrEMBL)
HMGN1ProteinP05114 (Uniprot-TrEMBL)
Hyperphosphorylated

RNA Pol II:Damaged DNA template:nascent mRNA

hybrid:TFIIH:ERCC6:ERCC8:DDB1:CUL4:RBX1
ComplexR-HSA-6781839 (Reactome)
Hyperphosphorylated

RNA Pol II:Damaged DNA template:nascent mRNA

hybrid:TFIIH:ERCC6
ComplexR-HSA-6781837 (Reactome)
Hyperphosphorylated

RNA Pol II:Damaged DNA template:nascent

mRNA hybrid:TFIIH
ComplexR-HSA-6781822 (Reactome)
INO80 ProteinQ9ULG1 (Uniprot-TrEMBL)
INO80 complexComplexR-HSA-5689568 (Reactome)
INO80B ProteinQ9C086 (Uniprot-TrEMBL)
INO80C ProteinQ6PI98 (Uniprot-TrEMBL)
INO80D ProteinQ53TQ3 (Uniprot-TrEMBL)
INO80E ProteinQ8NBZ0 (Uniprot-TrEMBL)
ISY1 ProteinQ9ULR0 (Uniprot-TrEMBL)
K63polyUb-C87-UBE2N ProteinP61088 (Uniprot-TrEMBL)
K63polyUb:C87-UBE2N:UBE2V2ComplexR-HSA-6790510 (Reactome)
LIG1 ProteinP18858 (Uniprot-TrEMBL)
LIG1,LIG3:XRCC1ComplexR-HSA-5690475 (Reactome)
LIG3 ProteinP49916 (Uniprot-TrEMBL)
MCRS1 ProteinQ96EZ8 (Uniprot-TrEMBL)
MNAT1 ProteinP51948 (Uniprot-TrEMBL)
MonoUb-K164-PCNA ProteinP12004 (Uniprot-TrEMBL)
NAD+MetaboliteCHEBI:57540 (ChEBI)
NAMMetaboliteCHEBI:17154 (ChEBI)
NFRKB ProteinQ6P4R8 (Uniprot-TrEMBL)
Open bubble-dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1, PAR-PARP2:CHD1LComplexR-HSA-6790517 (Reactome)
Open bubble damaged DNA template:trimmed nascent mRNA R-ALL-6782110 (Reactome)
PAR-DDB2 ProteinQ92466 (Uniprot-TrEMBL)
PAR-PARP1 ProteinP09874 (Uniprot-TrEMBL)
PAR-PARP1,PAR-PARP2 dimersComplexR-HSA-5651709 (Reactome)
PAR-PARP2 ProteinQ9UGN5 (Uniprot-TrEMBL)
PAR-UV-DDBComplexR-HSA-5696649 (Reactome)
PARP1 ProteinP09874 (Uniprot-TrEMBL)
PARP1,PARP2 dimersComplexR-HSA-5649884 (Reactome)
PARP2 ProteinQ9UGN5 (Uniprot-TrEMBL)
PCNA homotrimer,MonoUb:K164-PCNA homotrimerComplexR-HSA-6790532 (Reactome)
PCNA ProteinP12004 (Uniprot-TrEMBL)
PIAS1 ProteinO75925 (Uniprot-TrEMBL)
PIAS1,3ComplexR-HSA-6790455 (Reactome)
PIAS3 ProteinQ9Y6X2 (Uniprot-TrEMBL)
POLD,POLE R-HSA-5651800 (Reactome)
POLD,POLE,POLKComplexR-HSA-6790535 (Reactome)
POLD1 ProteinP28340 (Uniprot-TrEMBL)
POLD2 ProteinP49005 (Uniprot-TrEMBL)
POLD3 ProteinQ15054 (Uniprot-TrEMBL)
POLD4 ProteinQ9HCU8 (Uniprot-TrEMBL)
POLE ProteinQ07864 (Uniprot-TrEMBL)
POLE2 ProteinP56282 (Uniprot-TrEMBL)
POLE3 ProteinQ9NRF9 (Uniprot-TrEMBL)
POLE4 ProteinQ9NR33 (Uniprot-TrEMBL)
POLK ProteinQ9UBT6 (Uniprot-TrEMBL)
POLR2A ProteinP24928 (Uniprot-TrEMBL)
POLR2B ProteinP30876 (Uniprot-TrEMBL)
POLR2C ProteinP19387 (Uniprot-TrEMBL)
POLR2D ProteinO15514 (Uniprot-TrEMBL)
POLR2E ProteinP19388 (Uniprot-TrEMBL)
POLR2F ProteinP61218 (Uniprot-TrEMBL)
POLR2G ProteinP62487 (Uniprot-TrEMBL)
POLR2H ProteinP52434 (Uniprot-TrEMBL)
POLR2I ProteinP36954 (Uniprot-TrEMBL)
POLR2J ProteinP52435 (Uniprot-TrEMBL)
POLR2K ProteinP53803 (Uniprot-TrEMBL)
POLR2L ProteinP62875 (Uniprot-TrEMBL)
PPIE ProteinQ9UNP9 (Uniprot-TrEMBL)
PPiMetaboliteCHEBI:29888 (ChEBI)
PRPF19 ProteinQ9UMS4 (Uniprot-TrEMBL)
Partially open bubble damaged DNA template:trimmed nascent mRNA R-ALL-9684123 (Reactome)
PiMetaboliteCHEBI:43474 (ChEBI)
RAD23A ProteinP54725 (Uniprot-TrEMBL)
RAD23B ProteinP54727 (Uniprot-TrEMBL)
RAD23ComplexR-HSA-5688130 (Reactome)
RBX1 ProteinP62877 (Uniprot-TrEMBL)
RFC HeteropentamerComplexR-HSA-68436 (Reactome)
RFC1 ProteinP35251 (Uniprot-TrEMBL)
RFC2 ProteinP35250 (Uniprot-TrEMBL)
RFC3 ProteinP40938 (Uniprot-TrEMBL)
RFC4 ProteinP35249 (Uniprot-TrEMBL)
RFC5 ProteinP40937 (Uniprot-TrEMBL)
RNA

Polymerase II holoenzyme complex

(hyperphosphorylated)
ComplexR-HSA-109909 (Reactome)
RNA Polymerase II

holoenzyme complex

(unphosphorylated)
ComplexR-HSA-113401 (Reactome)
RNF111ProteinQ6ZNA4 (Uniprot-TrEMBL)
RPA heterotrimerComplexR-HSA-68462 (Reactome)
RPA1 ProteinP27694 (Uniprot-TrEMBL)
RPA2 ProteinP15927 (Uniprot-TrEMBL)
RPA3 ProteinP35244 (Uniprot-TrEMBL)
RPS27A(1-76) ProteinP62979 (Uniprot-TrEMBL)
RUVBL1 ProteinQ9Y265 (Uniprot-TrEMBL)
SSB-dsDNA R-HSA-110340 (Reactome)
SSB-dsDNA:trimmed nascent mRNA R-ALL-6782212 (Reactome)
SUMO1 ProteinP63165 (Uniprot-TrEMBL)
SUMO1,2,3:UBE2IComplexR-HSA-6790471 (Reactome)
SUMO1-C93-UBE2I ProteinP63279 (Uniprot-TrEMBL)
SUMO2 ProteinP61956 (Uniprot-TrEMBL)
SUMO2-C93-UBE2I ProteinP63279 (Uniprot-TrEMBL)
SUMO3 ProteinP55854 (Uniprot-TrEMBL)
SUMO3-C93-UBE2I ProteinP63279 (Uniprot-TrEMBL)
TC-NER

incision complex: 5'-incised damaged DNA:trimmed nascent

mRNA:(PCNA:POLD,POLE), (MonoUb:K164-PCNA:POLK):RPA:RFC
ComplexR-HSA-6782219 (Reactome)
TC-NER

post-incision

complex:SSB-dsDNA:trimmed nascent mRNA: (PCNA:POLD,POLE), (MonoUb:K164-PCNA:POLK):RPA:RFC
ComplexR-HSA-6782220 (Reactome)
TC-NER

post-incision complex:incised DNA without lesion:trimmed nascent

mRNA:PCNA:(PCNA:POLD,POLE),(MonoUb:K164-PCNA:POLK):RPA:RFC
ComplexR-HSA-6782222 (Reactome)
TC-NER

pre-incision complex:Open bubble damaged DNA

template:RPA:ERCC5:trimmed nascent mRNA
ComplexR-HSA-6782134 (Reactome)
TC-NER incision

complex:5'-incised damaged DNA:trimmed

nascent mRNA
ComplexR-HSA-6782205 (Reactome)
TC-NER incision complexComplexR-HSA-6782142 (Reactome)
TC-NER post-incision

complex:dsDNA with transcription

bubble
ComplexR-HSA-6782230 (Reactome)
TC-NER pre-incision

complex:Open bubble damaged DNA template:trimmed

nascent mRNA
ComplexR-HSA-6782111 (Reactome)
TC-NER pre-incision

complex:Partially open bubble damaged DNA template:trimmed

nascent mRNA
ComplexR-HSA-9684117 (Reactome)
TC-NER pre-incision complexComplexR-HSA-6782066 (Reactome)
TCEA1 ProteinP23193 (Uniprot-TrEMBL)
TCEA1ProteinP23193 (Uniprot-TrEMBL)
TFIIH CoreComplexR-HSA-5689624 (Reactome)
TFIIHComplexR-HSA-109634 (Reactome)
TFPT ProteinP0C1Z6 (Uniprot-TrEMBL)
UBA52(1-76) ProteinP62987 (Uniprot-TrEMBL)
UBB(1-76) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(153-228) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(77-152) ProteinP0CG47 (Uniprot-TrEMBL)
UBC(1-76) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(153-228) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(229-304) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(305-380) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(381-456) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(457-532) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(533-608) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(609-684) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(77-152) ProteinP0CG48 (Uniprot-TrEMBL)
UBE2I-G92-SUMO3 ProteinP55854 (Uniprot-TrEMBL)
UBE2I-G93-SUMO2 ProteinP61956 (Uniprot-TrEMBL)
UBE2I-G97-SUMO1 ProteinP63165 (Uniprot-TrEMBL)
UBE2IProteinP63279 (Uniprot-TrEMBL)
UBE2N ProteinP61088 (Uniprot-TrEMBL)
UBE2N:UBE2V2ComplexR-HSA-5682542 (Reactome)
UBE2V2 ProteinQ15819 (Uniprot-TrEMBL)
USP45ProteinQ70EL2 (Uniprot-TrEMBL)
USP7 ProteinQ93009 (Uniprot-TrEMBL)
UV-DDB:COP9 SignalosomeComplexR-HSA-5697031 (Reactome)
UVSSA ProteinQ2YD98 (Uniprot-TrEMBL)
UVSSA:USP7ComplexR-HSA-6781845 (Reactome)
Ub,SUMO,K63polyUb-XPC ProteinQ01831 (Uniprot-TrEMBL)
Ub,SUMO,K63polyUb:XPC:RAD23:CETN2ComplexR-HSA-6790519 (Reactome)
Ub,SUMO-XPC ProteinQ01831 (Uniprot-TrEMBL)
Ub,SUMO:XPC:RAD23:CETN2:Open bubble-dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1, PAR-PARP2:CHD1LComplexR-HSA-6790468 (Reactome)
Ub,p-S2,S5-POLR2A ProteinP24928 (Uniprot-TrEMBL)
Ub-139-UBB(77-152) ProteinP0CG47 (Uniprot-TrEMBL)
Ub-139-UBC(77-152) ProteinP0CG48 (Uniprot-TrEMBL)
Ub-215-UBB(153-228) ProteinP0CG47 (Uniprot-TrEMBL)
Ub-215-UBC(153-228) ProteinP0CG48 (Uniprot-TrEMBL)
Ub-291-UBC(229-304) ProteinP0CG48 (Uniprot-TrEMBL)
Ub-367-UBC(305-380) ProteinP0CG48 (Uniprot-TrEMBL)
Ub-443-UBC(381-456) ProteinP0CG48 (Uniprot-TrEMBL)
Ub-519-UBC(457-532) ProteinP0CG48 (Uniprot-TrEMBL)
Ub-595-UBC(533-608) ProteinP0CG48 (Uniprot-TrEMBL)
Ub-63-RPS27A(1-76) ProteinP62979 (Uniprot-TrEMBL)
Ub-63-UBA52(1-76) ProteinP62987 (Uniprot-TrEMBL)
Ub-63-UBB(1-76) ProteinP0CG47 (Uniprot-TrEMBL)
Ub-63-UBC(1-76) ProteinP0CG48 (Uniprot-TrEMBL)
Ub-671-UBC(609-684) ProteinP0CG48 (Uniprot-TrEMBL)
Ub-ERCC1 ProteinP07992 (Uniprot-TrEMBL)
Ub-ERCC6 ProteinQ03468 (Uniprot-TrEMBL)
Ub-XPC ProteinQ01831 (Uniprot-TrEMBL)
Ub:ERCC1ComplexR-HSA-5696466 (Reactome)
Ub:ERCC6ComplexR-HSA-6781849 (Reactome)
Ub:XPC:RAD23:CETN2:Distorted dsDNA:PAR-UV-DDB:PAR-PARP1,PAR-PARP2ComplexR-HSA-5696681 (Reactome)
Ub:XPC:RAD23:CETN2:Distorted dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1,PAR-PARP2:CHD1LComplexR-HSA-5696652 (Reactome)
Ub:XPC:RAD23:CETN2:Distorted dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1,PAR-PARP2ComplexR-HSA-5689300 (Reactome)
Ub:XPC:RAD23:CETN2:Distorted dsDNA:PAR-UV-DDB:TFIIH:PAR-PARP1,PAR-PARP2ComplexR-HSA-5689862 (Reactome)
Ub:XPC:RAD23:CETN2:Distorted dsDNA:UV-DDB:PARP1,PARP2ComplexR-HSA-5696660 (Reactome)
Ub:XPC:RAD23:CETN2:Distorted dsDNA:UV-DDBComplexR-HSA-6782948 (Reactome)
Ub:XPC:RAD23:CETN2:Open bubble-dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1,PAR-PARP2:CHD1LComplexR-HSA-5691018 (Reactome)
UbComplexR-HSA-68524 (Reactome)
Ubiquitinated,hyperphosphorylated RNA Pol II:Damaged DNA template:nascent mRNA hybrid:TFIIH:Ub:ERCC6:ERCC8:DDB1:CUL4:RBX1:UVSSA:USP7:XAB2 complex:XPA:TCEA1:HMGN1:EP300ComplexR-HSA-6782063 (Reactome)
Ubiquitinated,hyperphosphorylated RNA Pol II:Damaged DNA template:nascent mRNA hybrid:TFIIH:Ub:ERCC6:ERCC8:DDB1:CUL4:RBX1ComplexR-HSA-6781866 (Reactome)
XAB2 ProteinQ9HCS7 (Uniprot-TrEMBL)
XAB2 complexComplexR-HSA-6781957 (Reactome)
XPA ProteinP23025 (Uniprot-TrEMBL)
XPAProteinP23025 (Uniprot-TrEMBL)
XPC ProteinQ01831 (Uniprot-TrEMBL)
XPC:RAD23:CETN2:Distorted dsDNA:UV-DDBComplexR-HSA-5691012 (Reactome)
XPC:RAD23:CETN2ComplexR-HSA-5691010 (Reactome)
XPCProteinQ01831 (Uniprot-TrEMBL)
XRCC1 ProteinP18887 (Uniprot-TrEMBL)
YY1 ProteinP25490 (Uniprot-TrEMBL)
ZNF830 ProteinQ96NB3 (Uniprot-TrEMBL)
dNTPMetaboliteCHEBI:16516 (ChEBI)
damaged DNA substrate:nascent mRNA hybrid R-ALL-110291 (Reactome)
damaged DNA with 5' incision R-ALL-5691056 (Reactome)
damaged DNA with open bubble structure R-ALL-109944 (Reactome)
dsDNA with transcription bubble R-ALL-6782229 (Reactome)
dsDNAR-HSA-5649637 (Reactome)
excised DNA fragment with lesionR-ALL-109960 (Reactome)
incised DNA without lesion R-ALL-109961 (Reactome)
incised DNA without lesion:trimmed nascent mRNA R-ALL-6782213 (Reactome)
mRNAR-HSA-6782236 (Reactome)
p-S2,S5-POLR2A ProteinP24928 (Uniprot-TrEMBL) The C-terminal domain (CTD) of POLR2A contains about 52 repeats of the consensus heptad YSPTSPS. Serines-2 and 5 of the heptads are phosphorylated in RNA polymerase II initiating transcription of protein coding genes. The exact repeats that are phosphorylated are not known.
ribonucleoside triphosphateMetaboliteCHEBI:17972 (ChEBI)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
(PCNA:POLD,POLE), (MonoUb:K164-PCNA:POLK):RPA:RFC:Incised DNA without lesionArrowR-HSA-5690988 (Reactome)
(PCNA:POLD,POLE), (MonoUb:K164-PCNA:POLK):RPA:RFC:Incised DNA without lesionR-HSA-5691001 (Reactome)
(PCNA:POLD,POLE), (MonoUb:K164-PCNA:POLK):RPA:RFC:Incised DNA without lesionmim-catalysisR-HSA-5691001 (Reactome)
(PCNA:POLD,POLE), (MonoUb:K164-PCNA:POLK):RPA:RFC:SSB-dsDNAArrowR-HSA-5691001 (Reactome)
(PCNA:POLD,POLE), (MonoUb:K164-PCNA:POLK):RPA:RFC:SSB-dsDNAR-HSA-5690997 (Reactome)
(PCNA:POLD,POLE), (MonoUb:K164-PCNA:POLK):RPA:RFCArrowR-HSA-5690997 (Reactome)
(PCNA:POLD,POLE), (MonoUb:K164-PCNA:POLK):RPA:RFCArrowR-HSA-6782227 (Reactome)
ADPArrowR-HSA-5690996 (Reactome)
ADPArrowR-HSA-6782131 (Reactome)
ADPArrowR-HSA-9684118 (Reactome)
ATPR-HSA-5690996 (Reactome)
ATPR-HSA-6782131 (Reactome)
ATPR-HSA-9684118 (Reactome)
CAKArrowR-HSA-5689861 (Reactome)
CETN2R-HSA-5691004 (Reactome)
CHD1LArrowR-HSA-5690988 (Reactome)
CHD1LR-HSA-5696670 (Reactome)
COP9 signalosomeArrowR-HSA-5691006 (Reactome)
COP9 signalosomeArrowR-HSA-6781833 (Reactome)
Damaged

dsDNA with open transcription

bubble:Hyperphosphorylated RNA Pol II:TFIIH
ArrowR-HSA-6781818 (Reactome)
Damaged

dsDNA with open transcription

bubble:Hyperphosphorylated RNA Pol II:TFIIH
R-HSA-6781824 (Reactome)
Damaged

dsDNA with open transcription

bubble:Hyperphosphorylated RNA Pol II:TFIIH
mim-catalysisR-HSA-6781824 (Reactome)
Distorted dsDNAR-HSA-5691006 (Reactome)
Distorted dsDNAR-HSA-6781818 (Reactome)
ELLArrowR-HSA-6782234 (Reactome)
EP300ArrowR-HSA-6782234 (Reactome)
EP300R-HSA-6782004 (Reactome)
ERCC1:ERCC4ArrowR-HSA-109955 (Reactome)
ERCC1:ERCC4ArrowR-HSA-5690988 (Reactome)
ERCC1:ERCC4ArrowR-HSA-6782224 (Reactome)
ERCC1:ERCC4R-HSA-5690991 (Reactome)
ERCC1:ERCC4R-HSA-6782141 (Reactome)
ERCC1ArrowR-HSA-5696465 (Reactome)
ERCC1R-HSA-109955 (Reactome)
ERCC4R-HSA-109955 (Reactome)
ERCC5ArrowR-HSA-5690988 (Reactome)
ERCC5ArrowR-HSA-6782224 (Reactome)
ERCC5R-HSA-5689317 (Reactome)
ERCC5R-HSA-6782138 (Reactome)
ERCC6R-HSA-6781840 (Reactome)
ERCC8:DDB1:CUL4:RBX1:COP9 SignalosomeR-HSA-6781833 (Reactome)
ERCC8:DDB1:CUL4:RBX1ArrowR-HSA-6782234 (Reactome)
GG-NER

incision complex:5'-incised damaged

DNA:(PCNA:POLD,POLE),(MonoUb:K164-PCNA:POLK):RPA:RFC
ArrowR-HSA-5690213 (Reactome)
GG-NER

incision complex:5'-incised damaged

DNA:(PCNA:POLD,POLE),(MonoUb:K164-PCNA:POLK):RPA:RFC
R-HSA-5690988 (Reactome)
GG-NER

incision complex:5'-incised damaged

DNA:(PCNA:POLD,POLE),(MonoUb:K164-PCNA:POLK):RPA:RFC
mim-catalysisR-HSA-5690988 (Reactome)
GG-NER incision

complex:5'-incised

damaged DNA
ArrowR-HSA-5690990 (Reactome)
GG-NER incision

complex:5'-incised

damaged DNA
R-HSA-5690213 (Reactome)
GG-NER incision

complex:Open bubble

dsDNA
ArrowR-HSA-5690991 (Reactome)
GG-NER incision

complex:Open bubble

dsDNA
R-HSA-5690990 (Reactome)
GG-NER incision

complex:Open bubble

dsDNA
mim-catalysisR-HSA-5690990 (Reactome)
GG-NER pre-incision

complex:Open

bubble-dsDNA
ArrowR-HSA-5689317 (Reactome)
GG-NER pre-incision

complex:Open

bubble-dsDNA
R-HSA-5690991 (Reactome)
H2OR-HSA-5696465 (Reactome)
H2OR-HSA-6782069 (Reactome)
HMGN1ArrowR-HSA-6782234 (Reactome)
HMGN1R-HSA-6782004 (Reactome)
Hyperphosphorylated

RNA Pol II:Damaged DNA template:nascent mRNA

hybrid:TFIIH:ERCC6:ERCC8:DDB1:CUL4:RBX1
ArrowR-HSA-6781833 (Reactome)
Hyperphosphorylated

RNA Pol II:Damaged DNA template:nascent mRNA

hybrid:TFIIH:ERCC6:ERCC8:DDB1:CUL4:RBX1
R-HSA-6781867 (Reactome)
Hyperphosphorylated

RNA Pol II:Damaged DNA template:nascent mRNA

hybrid:TFIIH:ERCC6:ERCC8:DDB1:CUL4:RBX1
mim-catalysisR-HSA-6781867 (Reactome)
Hyperphosphorylated

RNA Pol II:Damaged DNA template:nascent mRNA

hybrid:TFIIH:ERCC6
ArrowR-HSA-6781840 (Reactome)
Hyperphosphorylated

RNA Pol II:Damaged DNA template:nascent mRNA

hybrid:TFIIH:ERCC6
R-HSA-6781833 (Reactome)
Hyperphosphorylated

RNA Pol II:Damaged DNA template:nascent

mRNA hybrid:TFIIH
ArrowR-HSA-6781824 (Reactome)
Hyperphosphorylated

RNA Pol II:Damaged DNA template:nascent

mRNA hybrid:TFIIH
R-HSA-6781840 (Reactome)
INO80 complexArrowR-HSA-5691006 (Reactome)
K63polyUb:C87-UBE2N:UBE2V2R-HSA-6790487 (Reactome)
LIG1,LIG3:XRCC1mim-catalysisR-HSA-5690997 (Reactome)
LIG1,LIG3:XRCC1mim-catalysisR-HSA-6782227 (Reactome)
NAD+R-HSA-5696655 (Reactome)
NAMArrowR-HSA-5696655 (Reactome)
Open bubble-dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1, PAR-PARP2:CHD1LArrowR-HSA-6790487 (Reactome)
Open bubble-dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1, PAR-PARP2:CHD1LR-HSA-5689317 (Reactome)
PAR-PARP1,PAR-PARP2 dimersArrowR-HSA-5690988 (Reactome)
PAR-UV-DDBArrowR-HSA-5690988 (Reactome)
PARP1,PARP2 dimersR-HSA-5696664 (Reactome)
PCNA homotrimer,MonoUb:K164-PCNA homotrimerR-HSA-5690213 (Reactome)
PCNA homotrimer,MonoUb:K164-PCNA homotrimerR-HSA-6782211 (Reactome)
PIAS1,3mim-catalysisR-HSA-6790454 (Reactome)
POLD,POLE,POLKR-HSA-5690213 (Reactome)
POLD,POLE,POLKR-HSA-6782211 (Reactome)
PPiArrowR-HSA-5691001 (Reactome)
PPiArrowR-HSA-6781824 (Reactome)
PPiArrowR-HSA-6782208 (Reactome)
PiArrowR-HSA-5690996 (Reactome)
PiArrowR-HSA-6782131 (Reactome)
PiArrowR-HSA-9684118 (Reactome)
R-HSA-109955 (Reactome) ERCC1 binds ERCC4 (XPF) to form a heterodimeric ERCC1:ERCC4 (ERCC1:XPF) complex with a DNA endonuclease activity, where ERCC4 is the catalytic subunit. Suitable substrates for the ERCC1:ERCC4 endonuclease are single strand DNA (ssDNA) and ssDNA region of a duplex DNA with an open bubble structure (Park et al. 1995).
R-HSA-5689317 (Reactome) Once an open bubble structure is generated in damaged dsDNA through a DNA helicase activity of the TFIIH complex, the RPA heterotrimer composed of RPA1, RPA2 and RPA3, coats the undamaged single strand DNA (ssDNA) (de Laat et al. 1998), thereby protecting it from incision and enabling the correct positioning of the NER endonucleases. The interaction of RPA with XPA facilitates RPA recruitment to the global genome nucleotide excision repair (GG-NER) site (He et al. 1995, Ikegami et al. 1998). A DNA endonuclease ERCC5 (XPG) is recruited to the GG-NER site, 3' to the DNA damage, through its interaction with the TFIIH complex (Dunand-Sauthier et al. 2005, Zotter et al. 2006, Ito et al. 2007) and the RPA heterotrimer (de Laat et al. 1998).
R-HSA-5689861 (Reactome) XPA binds the DNA damage site through interaction with the TFIIH complex subunit GTF2H5 (TTDA) (Ziani et al. 2014), and also interacts with the DDB2 subunit of the UV-DDB complex (Wakasugi et al. 2001, Wakasugi et al. 2009, Takedachi et al. 2010). PARylated PARP1 (or possibly PARP2) (King et al. 2012) facilitates XPA association with chromatin. Binding of XPA is accompanied by the release of the CAK subcomplex from the TFIIH complex (Coin et al. 2008).
R-HSA-5690213 (Reactome) The DNA repair synthesis complex, consisting of PCNA, RFC, RPA and polymerase delta (POLD) or epsilon (POLE) complexes, or DNA translesion synthesis polymerase kappa (POLK) (Ogi et al. 2010), is formed at the nucleotide excision repair (NER) site following the incision of the damaged DNA strand 5' to the lesion by the ERCC1:ERCC4 (ERCC1:XPF) complex. 3' incision by XPG (ERCC5) is not required for the loading of the DNA polymerases and may not be required for the initiation of NER-mediated DNA synthesis (Staresincic et al. 2009). XPG and RPA promote the assembly of the DNA synthesis complex at the NER site (Mocquet et al. 2008).
R-HSA-5690988 (Reactome) In global genome nucleotide excision repair (GG-NER), as well as transcription-coupled nucleotide excision repair (TC-NER), the cleavage of the damaged DNA strand 3' to the site of damage is carried out by a DNA endonuclease XPG (ERCC5). While the DNA repair synthesis may be initiated prior to the 3' incision (Staresincic et al. 2009), the components of the incision complex probably dissociate from the NER site shortly after the replicative complex assembly and 3' incision (Overmeer et al. 2011). The exception is the RPA heterotrimer, which is a constituent of the DNA synthesis complex, and also coats the undamaged DNA strand, thereby protecting it from endonucleolytic cleavage.
R-HSA-5690990 (Reactome) In global genome nucleotide excision repair (GG-NER), just like in transcription-coupled nucleotide excision repair (TC-NER), the cleavage of the damaged strand of DNA 5' to the site of damage occurs at the junction of single-stranded DNA and double-stranded DNA that is formed when the DNA duplex is unwound. The 5' incision is carried out by the ERCC1:XPF (ERCC1:ERCC4) complex and precedes the 3' incision (Staresincic et al. 2009).
R-HSA-5690991 (Reactome) ERCC1:ERCC4 (ERCC1:XPF) DNA endonuclease complex binds 5' to the DNA damage at global genome nucleotide excision repair (GG-NER) sites to form the incision complex. Binding of ERCC5 (XPG) to the NER site precedes the recruitment of ERCC1:ERCC4 (Riedl et al. 2003). ERCC1 directly interacts with XPA, and this interaction is necessary for the loading of ERCC1:ERCC4 to the open bubble structure in damaged dsDNA and the progression of GG-NER (Tsodikov et al. 2007, Orelli et al. 2010).
R-HSA-5690996 (Reactome) Two DNA helicases XPB (ERCC3) and XPD (ERCC2), which are part of the TFIIH complex, unwind the distorted DNA duplex around the lesion to form an open bubble structure that exposes the damaged site. The helicase activity of the TFIIH complex is stimulated by the presence of XPA and the XPC:RAD23:CETN2 complex (Winkler et al. 2001). The 5'->3' directed helicase activity of ERCC2 (Kuper et al. 2012) is crucial for unwinding of the distorted dsDNA during nucleotide excision repair (NER) (Coin et al. 2007). The 3'->5' directed DNA helicase ERCC3 contributes to dsDNA unwinding during NER through ATP hydrolysis (Coin et al. 2007). In addition to DNA unwinding, ERCC2 and ERCC3 verify the presence of DNA damage (Oksenych et al. 2009, Mathieu et al. 2010, Mathieu et al. 2013). Verification of DNA damage also involves XPA (Camenisch et al. 2006). The binding site of XPC determines which DNA strand is selected by ERCC2 to verify the presence of lesions (Sugasawa et al. 2009).
R-HSA-5690997 (Reactome) The nucleotide excision repair (NER) is completed when the newly synthesized fragment is ligated to the incised DNA strand, thus closing the single stranded nick (SSB). Two DNA ligases, LIG1 and LIG3 (as part of the LIG3:XRCC1 complex) can perform the ligation in global genome NER (GG-NER), as well as in transcription-coupled NER (TC-NER). The choice of NER DNA ligase depends on the DNA polymerase involved in the repair synthesis and on the stage of the cell cycle (Moser et al. 2007).
R-HSA-5691000 (Reactome) Transcription factor II H (TFIIH) complex is recruited to DNA damage sites after the damage is recognized by the XPC:RAD23:CETN2 complex and the UV-DDB complex (DDB1:DDB2) (Volker et al. 2001, Araujo and Wood 1999).

TFIIH consists of ten subunits organized into a ring-like structure (Schultz et al. 2000). The TFIIH core, also forming a ring-like structure, includes a DNA helicase ERCC3 (XPB), GTF2H1 (BTF2-p62), GTF2H2 (BTF2-p44), GTF2H3 (BTF2-p34) and GTF2H4 (BTF2-p52). GTF2H4 directly interacts with ERCC3 and anchors it to the TFIIH complex (Jawhari et al. 2002). Another DNA helicase, ERCC2 (XPD) is anchored to the TFIIH complex by binding to the GTF2H2 subunit (Coin et al. 1998). The CDK-activating kinase (CAK) complex, consisting of CCNH (cyclin H), CDK7 and MNAT1 (MAT1) is included in the TFIIH complex through an interaction with ERCC2 (Reardon et al. 1996, Rossignol et al. 1997). The tenth subunit, GTF2H5 (TTDA, TFB5, BTF2-p5) is important for the stability of the TFIIH complex (Giglia-Mari et al. 2004). The TFIIH complex binds the DNA damage site after XPC:RAD23:CETN2 complex recognizes the damage (Volker et al. 2001, Riedl et al. 2003), and the ERCC3 and GTF2H1 subunits of TFIIH directly interact with XPC (Yokoi et al. 2003).

R-HSA-5691001 (Reactome) In global genome nucleotide excision repair (GG-NER), as well as transcription-coupled nucleotide excision repair (TC-NER), the DNA synthesis complex consisting of PCNA, RPA, RFC and polymerase delta (POLD) or epsilon (POLE) complexes performs DNA repair synthesis after the damaged DNA strand is incised 5' to the lesion by the endonuclease complex ERCC1:ERCC4 (ERCC1:XPF) and 3' to the lesion by the endonuclease XPG (ERCC5). Depending on damage-induced PCNA monoubiquitination, DNA polymerase kappa (POLK) is also involved in gap-filling DNA synthesis during nucleotide excision repair (NER) (Balajee et al. 1998, Staresincic et al. 2009, Ogi et al. 2010, Overmeer et al. 2011).
R-HSA-5691004 (Reactome) XPC is mutated in individuals with xeroderma pigmentosum from genetic Complementation Group C (XP-C). It forms a tight complex with RAD23B (HR23B) or, to a lesser extent, RAD23A (HR23A), two human homologs of yeast Rad23 (Masutani et al. 1994, Ng et al. 2003). CETN2 (centrin 2, CEN2) is also part of the XPC complex with RAD23 (Araki et al. 2001, Nishi et al. 2005).
R-HSA-5691006 (Reactome) XPC, in complex with RAD23B or RAD23A and CETN2, employs a two-stage process to recognize a distorted DNA helix. In the first stage, XPC rapidly probes dsDNA, which is promoted by a DNA repulsive action of a negatively charged beta-turn extension of XPC, located in the vicinity of the XPC DNA-binding domain. In the second stage, the DNA binding domain, consisting of two beta hairpins, binds non-hydrogen bonded bases in dsDNA (Camenisch et al. 2009). Rad4, the yeast ortholog of XPC, recognizes lesions that thermodynamically disrupt normal Watson-Crick base pairing. Rad4 inserts a beta-hairpin through the DNA duplex, causing damaged base pairs to flip out of the double helix. Rad4 associates with the undamaged strand, whereas the DNA strand that contains damaged nucleotides becomes distorted (Min and Pavletich 2007).

Binding of the XPC:RAD23:CETN2 complex to distorted DNA is enhanced in the presence of the DDB1:DDB2 complex, also known as the UV-DDB complex. The UV-DDB complex preferentially binds UV-generated lesions, such as pyrimidine-pyrimidone photodimers (6-4 PPDs) and cyclobutane pyrimidine dimers (CPDs), but also recognizes DNA with apurinic/apyrimidinic (AP) sites, and 2-3 bp mismatches (Fujiwara et al. 1999, Wittschieben et al. 2005). The DDB2 subunit of the UV-DDB complex is a WD40 repeat beta-propeller protein. The beta-propeller domain of DDB2 binds the damaged DNA strand (Scrima et al. 2008). The UV-DDB complex is part of a larger ubiquitin ligase complex that, besides DDB1 and DDB2, also contains CUL4A or CUL4B and RBX1 (Groisman et al. 2003, Sugasawa et al. 2005). In the case of 6-4 PPDs and CPDs, UV-DDB binding to damaged DNA probably precedes the binding of the XPC:RAD23:CETN2 complex. However, in the case of 6-4 PPDs, the XPC:RAD23:CETN2 complex may also recognize damaged DNA in the absence of the UV-DDB complex (Fitch et al. 2003, Moser et al. 2005, Wang et al. 2004), but the UV-DDB complex may be important for retention of DNA repair proteins at the DNA damage site (Oh et al. 2011).

The INO80 chromatin remodelling complex positively regulates GG-NER. INO80 and ACTR5 (ARP5) subunits of the INO80 complex are enriched at GG-NER sites, probably via interaction with DDB1. Chromatin relaxation by the INO80 complex at DNA damage site may be necessary for XPC recruitment (Jiang et al. 2010). In yeast, the interaction between INO80 and the orthologs of XPC and RAD23 has been reported and it was suggested that this interaction is important for the restoration of chromatin structure after GG-NER completion (Sarkar et al. 2010).

R-HSA-5696465 (Reactome) USP45 ubiquitin protease, mutated in prostate cancer and B-cell lymphoma, deubiquitinates ERCC1. While the mechanism and timing of ERCC1 ubiquitination are not known, deubiquitination of ERCC1 by USP45 enables ERCC1 recruitment to DNA damage sites in nucleotide excision repair (NER) and repair of interstrand cross-links (ICLR) (Perez-Oliva et al. 2015).
R-HSA-5696655 (Reactome) PARP1 and/or PARP2 homo- or heterodimers recruited to global genomic nucleotide excision repair (GG-NER) site poly(ADP)ribosylate (PARylate) DDB2 and also progressively autoPARylate. PARylation promotes retention of DDB2 at DNA damage sites (Pines et al. 2012, Robu et al. 2013).
R-HSA-5696664 (Reactome) PARP1 (or PARP2) is recruited to global genomic nucleotide excision repair (GG-NER) site through interaction with DDB2 and, probably, distorted single strand DNA (Pines et al. 2012, Robu et al. 2013).
R-HSA-5696670 (Reactome) A chromatin remodeling enzyme CHD1L (ALC1) is recruited to DNA damage sites through interaction with PARylated PARP1 (or possibly PARP2) (Ahel et al. 2009) or PARylated DDB2 (Pines et al. 2012). CHD1L catalyzes PARP-stimulated nucleosome sliding and is needed for efficient PARP-dependent DNA repair (Ahel et al. 2009). CHD1L depletion or PARP inhibition impair global genomic nucleotide excision repair (GG-NER) of UV-induced DNA damage (Pines et al. 2012).
R-HSA-6781818 (Reactome) Once the transcription is initiated from a DNA template that contains an RNA polymerase II (RNA Pol II) promoter, RNA Pol II synthesizes mRNA in the presence of the elongation complex TFIIH until the damaged DNA base(s) is reached (Brueckner et al. 2007).
R-HSA-6781824 (Reactome) An active RNA polymerase II complex (RNA Pol II, POLR2) transcribes a damaged DNA template. Once damaged DNA bases, such as cyclobutane pyrimidine dimers (CPDs), enter the active site of the polymerase, RNA Pol II misincorporates a ribonucleotide into nascent mRNA, which blocks the translocation step and results in polymerase stalling. In the stalled complex, the lesion is inaccessible, while the RNA Pol II conformation is unchanged (Brueckner et al. 2007).
R-HSA-6781833 (Reactome) Cockayne syndrome protein A (ERCC8, also known as CSA) is recruited to a stalled RNA polymerase II complex (RNA Pol II) at a site of DNA damage in an ERCC6 (CSB) dependent manner (Fousteri et al. 2006). ERCC8 is part of an ubiquitin ligase complex that, in addition to ERCC8, also contains DDB1, CUL4 (CUL4A or CUL4B) and RBX1 (Groisman et al. 2003). The COP9 signalosome complex prevents the ubiquitin ligase activity of the ERCC8:DDB1:CUL4:RBX1 at the early steps after DNA damage induction (Groisman et al. 2003, Fischer et al. 2011).
R-HSA-6781840 (Reactome) Cockayne syndrome protein B (ERCC6, also known as CSB) binds RNA polymerase II complex (RNA Pol II) stalled at a DNA damage site (Fousteri et al. 2006).
R-HSA-6781867 (Reactome) The ubiquitin ligase complex ERCC8:DDB1:CUL4:RBX1 may ubiquitinate ERCC6 (CSB) (Groisman et al. 2006) at the later steps of TC-NER and may also be required in the ubiquitination of the RNA Pol II subunit POLR2A in response to damage (Bregman et al. 1996, Lee et al. 2002). Ubiquitination mediated by ERCC8 (CSA) containing ubiquitin ligase complex plays an important role in progression and termination of transcription-coupled nucleotide excision repair (TC-NER), although the mechanistic details are largely unknown.
R-HSA-6782004 (Reactome) In addition to ERCC6 (CSB) and the ERCC8 (CSA) ubiquitin ligase complex, several other proteins and protein complexes are loaded onto stalled RNA polymerase II (RNA Pol II) at DNA damage sites to form a pre-incision complex that operates in the transcription-coupled nucleotide excision repair (TC-NER).
XPA, which also participates in global genome nucleotide excision repair (GG-NER), is necessary for the progression of TC-NER (Furuta et al. 2002). XPA interacts with the GTF2H5 subunit of the TFIIH complex (Ziani et al. 2014). In GG-NER, XPA loading is accompanied by the release of the CAK subcomplex from TFIIH (Coin et al. 2008), but in TC-NER the CAK complex remains bound to the TC-NER site (Mourgues et al. 2013).
XAB2 protein exists in the complex with five other proteins, AQR, PRPF19, ZNF830, ISY1 and PPIE. The XAB2 complex, which is also involved in pre-mRNA splicing, loads onto stalled RNA Pol II site (Kuraoka et al. 2008) through the interaction of XAB2 with RNA Pol II, ERCC6, ERCC8 and XPA (Nakatsu et al. 2000). The AQR (aquarius) subunit of the XAB2 complex is an RNA-DNA helicase that processes R-loops. An R-loop is a structure formed by hybridization of a nascent mRNA with a DNA template. In the absence of AQR, TC-NER machinery processes R-loops into double strand breaks (Sollier et al. 2014).
TCEA1 (TFIIS) is a transcription elongation factor that facilitates partial digestion of the 3' protruding end of the nascent transcript by a stalled RNA Pol II, which is generated during the reverse translocation of RNA Pol II from the damage site, and allows the resumption of RNA synthesis once the DNA damage is removed (Donahue et al. 1994).
HMGN1, a non-histone high mobility group N nucleosome-binding protein, facilitates TC-NER probably by increasing accessibility of damaged DNA to repair machinery. HMGN1 is recruited at RNA Pol II/TC-NER sites in an ERCC8 (CSA)-dependent manner (Birger et al. 2003, Fousteri et al. 2006).
Histone acetyltransferase p300 (EP300) is recruited to stalled RNA Pol II/TC-NER complexes in an ERCC6-dependent manner, and probably acts to facilitate access of repair proteins to damaged DNA via chromatin remodeling (Fousteri et al. 2006).
UVSSA protein forms a complex with ubiquitin protease USP7. It is recruited to TC-NER sites via interaction with ubiquitinated RNA Pol II and ERCC6. The UVSSA:USP7 complex stabilizes ERCC6, preventing its proteasome-mediated degradation prior to TC-NER completion, and may de-ubiquitinate RNA Pol II after TC-NER is completed, to allow resumption of RNA synthesis (Nakazawa et al. 2012, Schwertman et al. 2012, Zhang et al. 2012, Fei and Chen 2012).
R-HSA-6782069 (Reactome) UVSSA stabilizes ERCC6 (CSB) during transcription-coupled nucleotide excision repair (TC-NER) by targeting ubiquitin protease USP7 to ubiquitinated ERCC6, thus preventing proteasome-mediated degradation of ERCC6. Mutations in UVSSA cause UV-sensitive syndrome (Nakazawa et al. 2012, Schwertman et al. 2012, Zhang et al. 2012, Fei and Chen 2012).
R-HSA-6782131 (Reactome) The DNA helicase XPD (ERCC2), which is part of the TFIIH complex, unwinds the distorted DNA duplex around the lesion to form an open bubble structure that exposes the damaged site. The 5'->3 directed helicase activity of ERCC2 (Kuper et al. 2012) together with the ATPase activity of the 3'->5' directed DNA helicase ERCC3 contribute to dsDNA unwinding during nucleotide excision repair (NER) (Coin et al. 2007). In transcription-coupled NER (TC-NER), the ATPase activity of TFIIH complex, related to its helicase activity, is in addition necessary for the incision of the damaged DNA strand. While the endonuclease ERCC5 (XPG) can bind stalled RNA polymerase II (RNA Pol II) at a transcription bubble, it cannot perform incision in the absence of the TFIIH ATPase activity (Sarker et al. 2005). The helicase activity of the TFIIH complex may allow backtracking of the RNA Pol II, similar to the UvrD helicase involved in TC-NER in E.coli. Pulling RNA Pol II backwards from the DNA damage site would resolve steric hindrance of the RNA Pol II complex with the TC-NER endonucleases (Epshtein et al. 2014). RNA Pol II backtracking is accompanied by a partial digestion of the nascent 3' protruding mRNA via the 3'->5' directed exonuclease activity of RNA Pol II, which is stimulated by TCEA1 (TFIIS) (Donahue et al. 1994). Partial transcript digestion and RNA Pol II backtracking move the transcription bubble away from the open bubble that contains the DNA damage site (reviewed by Hanawalt and Spivak 2008).
R-HSA-6782138 (Reactome) It has been suggested that, similar to the UvrD helicase involved in TC-NER in E.coli, the DNA helicase activity of TFIIH complex may facilitate damage-stalled RNA polymerase II (RNA Pol II) backtracking (Epshtein et al. 2014). RNA Pol II backtracking, together with the cleavage of the 3' protruding end of nascent mRNA, might promote the movement of the transcription bubble away from the transcription-coupled nucleotide excision repair (TC-NER) site, while an open bubble is created (Sarker et al. 2005, Hanawalt and Spivak 2008). Once the open bubble is generated, the RPA heterotrimer composed of RPA1, RPA2 and RPA3 coats the undamaged single strand DNA (ssDNA) (de Laat et al. 1998), thereby protecting it from endonucleases. The interaction of RPA with XPA facilitates RPA recruitment to the nucleotide excision repair (NER) site (He et al. 1995, Ikegami et al. 1998). A DNA endonuclease ERCC5 (XPG) is recruited to the TC-NER site through its interaction with the stalled RNA Pol II (Sarker et al. 2005), the TFIIH complex (Dunand-Sauthier et al. 2005, Zotter et al. 2006, Ito et al. 2007) and the RPA heterotrimer (de Laat et al. 1998).
R-HSA-6782141 (Reactome) ERCC1:ERCC4 (ERCC1:XPF) DNA endonuclease complex binds to the pre-incision complex at the transcription-coupled nucleotide excision repair (TC-NER) site to form the incision complex. Binding of ERCC5 (XPG) to the NER site precedes the recruitment of ERCC1:ERCC4 (Riedl et al. 2003). ERCC1 directly interacts with the XPA, and this interaction is necessary for the loading of ERCC1:ERCC4 to the open bubble structure in damaged dsDNA and the progression of TC-NER (Tsodikov et al. 2007, Orelli et al. 2010).
R-HSA-6782204 (Reactome) In transcription-coupled nucleotide excision repair (TC-NER), just like in global genome nucleotide excision repair (GG-NER), the cleavage of the damaged strand of DNA 5' to the site of damage occurs at the junction of single-stranded DNA and double-stranded DNA that is formed when the DNA duplex is unwound. The 5' incision is carried out by ERCC1:XPF (ERCC1:ERCC4) complex and precedes the 3' incision by ERCC5 (XPG) (Staresincic et al. 2009).
R-HSA-6782208 (Reactome) In transcription-coupled nucleotide excision repair (TC-NER), as well as in global genome nucleotide excision repair (GG-NER), the DNA synthesis complex (NER post-incision complex) consisting of PCNA, RPA, RFC and polymerase delta (POLD) or epsilon (POLE) complexes performs DNA repair synthesis after the damaged DNA strand is incised 5' to the lesion by the endonuclease complex ERCC1:ERCC4 (ERCC1:XPF) and 3' to the lesion by the endonuclease XPG (ERCC5). Depending on damage-induced PCNA monoubiquitination, DNA polymerase kappa (POLK) may also be involved in gap-filling DNA synthesis during nucleotide excision repair (NER) (Balajee et al. 1998, Staresincic et al. 2009, Ogi et al. 2010, Overmeer et al. 2011).
R-HSA-6782211 (Reactome) The DNA repair synthesis complex, consisting of PCNA, RFC, RPA and polymerase delta (POLD) or epsilon (POLE) complexes, or polymerase kappa (POLK), is formed at the transcription coupled nucleotide excision repair (TC-NER) site, as well as the global genome nucleotide excision repair (GG-NER) site, following the incision of the damaged DNA strand 5' to the lesion by the ERCC1:ERCC4 (ERCC1:XPF) complex. 3' incision by XPG (ERCC5) is not required for the loading of the DNA polymerases and may not be required for the initiation of NER-mediated DNA synthesis (Staresincic et al. 2009). XPG and RPA promote the assembly of the DNA synthesis complex at the NER site (Mocquet et al. 2008).
R-HSA-6782224 (Reactome) In transcription-coupled nucleotide excision repair (TC-NER), as well as in global genome nucleotide excision repair (GG-NER), the cleavage of the damaged DNA strand 3' to the site of damage is carried out by a DNA endonuclease XPG (ERCC5). While the NER-mediated DNA synthesis may be initiated prior to the 3' incision (Staresincic et al. 2009), the components of the incision complex probably dissociate from the NER site shortly after the DNA synthesis complex assembly and 3' incision (Overmeer et al. 2011). The exception is the RPA heterotrimer, which is a constituent of the NER post-incision complex, and also coats the undamaged DNA strand, thereby protecting it from endonucleolytic cleavage. RNA polymerase II-associated factors also remain bound to the TC-NER site.
R-HSA-6782227 (Reactome) The nucleotide excision repair (NER) is completed when the newly synthesized fragment is ligated to the incised DNA strand, thus sealing the single stranded nick (SSB). Two DNA ligases, LIG1 and LIG3 (as a part of LIG3:XRCC1 complex) can perform the ligation in transcription-coupled NER (TC-NER), as well as in global genome NER (GG-NER). The choice of NER DNA ligase depends on the DNA polymerase involved in repair synthesis and probably the stage of the cell cycle (Moser et al. 2007).
R-HSA-6782234 (Reactome) After DNA repair synthesis is completed at transcription-coupled nucleotide excision repair (TC-NER) sites, transcription resumes. A number of factors have been implicated in this process. ERCC6 (CSB) contains an ubiquitin-binding domain that is indispensable for its function in TC-NER and the restoration of damage-inhibited RNA synthesis (Anindya et al. 2010). The ubiquitin ligase activity of the ERCC8:DDB1:CUL4:RBX1 complex plays an important role in termination of TC-NER, possibly by targeting ERCC6 or its ubiquitinated partner for degradation and promoting dissociation of repair factors from the RNA polymerase II complex (Groisman et al. 2006, Vermeulen and Fousteri 2013). The ubiquitin protease complex composed of UVSSA and USP7 is also implicated in the recovery of RNA synthesis (RRS) (Nakazawa et al. 2012, Scwertman et al. 2012, Zhang et al. 2012, Fei and Chen 2012). ELL protein, recruited to the TFIIH complex, possibly as a component of the little elongation complex, is needed for RRS (Mourgues et al. 2013). Furthermore, histone chaperone FACT promotes accelerated histone exchange at TC-NER sites, allowing efficient progression of TC-NER and restoration of RNA synthesis after the repair of transcription blocking damages is completed (Dinant et al. 2013).
R-HSA-6782943 (Reactome) The role of UV-DDB-mediated ubiquitination in global genome nucleotide excision repair (GG-NER) has not been fully elucidated.

In the absence of DNA damage, the ubiquitin ligase activity of UV-DDB complex is inhibited by association with the COP9 signalosome (CSN complex), which dissociates from the UV-DDB complex upon binding to damaged DNA (Groisman et al. 2003, Fischer et al. 2011). Ubiquitination of XPC by UV-DDB promotes XPC retention at GG-NER sites, while progressive autoubiquitination of UV-DDB promotes the dissociation of UV-DDB from the DNA and may act as an intracellular signal (Sugasawa et al. 2005). The UV-DDB complex also ubiquitinates histones H2A, H3 and H4, which may trigger chromatin remodeling at DNA damage site and regulate the accessibility of damaged DNA to repair factors (Kapetanaki et al. 2006, Wang et al. 2006).

R-HSA-6790454 (Reactome) XPC undergoes SUMOylation following UV irradiation on several consensus SUMOylation sites (van Cuijk et al. 2015). SUMOylation of XPC probably succeeds the UV-DDB mediated ubiquitination of XPC, as the presence of both DDB2 and XPA is required for SUMOylation (Wang et al. 2005), but it has also been reported that SUMOylation of XPC was DDB2-independent (Akita et al. 2015). It is unclear whether XPC is modified by SUMO1 (Wang et al. 2005, Akita et al. 2015) or poly-SUMO2/3 (Poulsen et al. 2013). SUMO conjugases PIAS1 and PIAS3 both interact with XPC and may catalyze XPC SUMOylation (Akita et al. 2015).
R-HSA-6790487 (Reactome) SUMOylated XPC is recognized by the SUMO-targeted ubiquitin ligase RNF111 (Arcadia) that, together with the E2 ubiquitin conjugating complex of UBE2N (UBC13) and UBE2V2 (MMS2), generates K63-linked polyubiquitin chains on XPC (Poulsen et al. 2013) to efficiently release XPC from UV lesions (van Cuijk et al. 2015). The release of K63-polyubiquitinated XPC occurs from GG-NER pre-incision complexes that contain TFIIH and XPA and promotes optimal access/binding of ERCC5 (XPG) endonuclease to the pre-incision complex (van Cuijk et al. 2015). Successful binding of ERCC5 endonuclease 3' to the damage facilitates binding of the ERCC1:ERCC4 (ERCC1:XPF) endonuclease and progression of the NER reaction.
R-HSA-9684118 (Reactome) The DNA helicase XPB (ERCC3), which is part of the TFIIH complex, unwinds the distorted DNA duplex around the lesion to form an open bubble structure that exposes the damaged site. ERCC3 is a 3'->5' directed DNA helicase whose ATPase activity, together with the 5'->3 directed helicase activity of ERCC2 (Kuper et al. 2012), contributes to dsDNA unwinding during nucleotide excision repair (NER) (Coin et al. 2007). In transcription-coupled NER (TC-NER), the ATPase activity of TFIIH complex, related to its helicase activity, is in addition necessary for the incision of the damaged DNA strand. While the endonuclease ERCC5 (XPG) can bind stalled RNA polymerase II (RNA Pol II) at a transcription bubble, it cannot perform incision in the absence of the TFIIH ATPase activity (Sarker et al. 2005). The helicase activity of the TFIIH complex may allow backtracking of the RNA Pol II, similar to the UvrD helicase involved in TC-NER in E.coli. Pulling RNA Pol II backwards from the DNA damage site would resolve steric hindrance of the RNA Pol II complex with the TC-NER endonucleases (Epshtein et al. 2014). RNA Pol II backtracking is accompanied by a partial digestion of the nascent 3' protruding mRNA via the 3'->5' directed exonuclease activity of RNA Pol II, which is stimulated by TCEA1 (TFIIS) (Donahue et al. 1994). Partial transcript digestion and RNA Pol II backtracking move the transcription bubble away from the open bubble that contains the DNA damage site (reviewed by Hanawalt and Spivak 2008).
RAD23R-HSA-5691004 (Reactome)
RFC HeteropentamerR-HSA-5690213 (Reactome)
RFC HeteropentamerR-HSA-6782211 (Reactome)
RNA

Polymerase II holoenzyme complex

(hyperphosphorylated)
ArrowR-HSA-6782234 (Reactome)
RNA Polymerase II

holoenzyme complex

(unphosphorylated)
R-HSA-6781818 (Reactome)
RNF111mim-catalysisR-HSA-6790487 (Reactome)
RPA heterotrimerR-HSA-5689317 (Reactome)
RPA heterotrimerR-HSA-6782138 (Reactome)
SUMO1,2,3:UBE2IR-HSA-6790454 (Reactome)
TC-NER

incision complex: 5'-incised damaged DNA:trimmed nascent

mRNA:(PCNA:POLD,POLE), (MonoUb:K164-PCNA:POLK):RPA:RFC
ArrowR-HSA-6782211 (Reactome)
TC-NER

incision complex: 5'-incised damaged DNA:trimmed nascent

mRNA:(PCNA:POLD,POLE), (MonoUb:K164-PCNA:POLK):RPA:RFC
R-HSA-6782224 (Reactome)
TC-NER

incision complex: 5'-incised damaged DNA:trimmed nascent

mRNA:(PCNA:POLD,POLE), (MonoUb:K164-PCNA:POLK):RPA:RFC
mim-catalysisR-HSA-6782224 (Reactome)
TC-NER

post-incision

complex:SSB-dsDNA:trimmed nascent mRNA: (PCNA:POLD,POLE), (MonoUb:K164-PCNA:POLK):RPA:RFC
ArrowR-HSA-6782208 (Reactome)
TC-NER

post-incision

complex:SSB-dsDNA:trimmed nascent mRNA: (PCNA:POLD,POLE), (MonoUb:K164-PCNA:POLK):RPA:RFC
R-HSA-6782227 (Reactome)
TC-NER

post-incision complex:incised DNA without lesion:trimmed nascent

mRNA:PCNA:(PCNA:POLD,POLE),(MonoUb:K164-PCNA:POLK):RPA:RFC
ArrowR-HSA-6782224 (Reactome)
TC-NER

post-incision complex:incised DNA without lesion:trimmed nascent

mRNA:PCNA:(PCNA:POLD,POLE),(MonoUb:K164-PCNA:POLK):RPA:RFC
R-HSA-6782208 (Reactome)
TC-NER

post-incision complex:incised DNA without lesion:trimmed nascent

mRNA:PCNA:(PCNA:POLD,POLE),(MonoUb:K164-PCNA:POLK):RPA:RFC
mim-catalysisR-HSA-6782208 (Reactome)
TC-NER

pre-incision complex:Open bubble damaged DNA

template:RPA:ERCC5:trimmed nascent mRNA
ArrowR-HSA-6782138 (Reactome)
TC-NER

pre-incision complex:Open bubble damaged DNA

template:RPA:ERCC5:trimmed nascent mRNA
R-HSA-6782141 (Reactome)
TC-NER incision

complex:5'-incised damaged DNA:trimmed

nascent mRNA
ArrowR-HSA-6782204 (Reactome)
TC-NER incision

complex:5'-incised damaged DNA:trimmed

nascent mRNA
R-HSA-6782211 (Reactome)
TC-NER incision complexArrowR-HSA-6782141 (Reactome)
TC-NER incision complexR-HSA-6782204 (Reactome)
TC-NER incision complexmim-catalysisR-HSA-6782204 (Reactome)
TC-NER post-incision

complex:dsDNA with transcription

bubble
ArrowR-HSA-6782227 (Reactome)
TC-NER post-incision

complex:dsDNA with transcription

bubble
R-HSA-6782234 (Reactome)
TC-NER pre-incision

complex:Open bubble damaged DNA template:trimmed

nascent mRNA
ArrowR-HSA-9684118 (Reactome)
TC-NER pre-incision

complex:Open bubble damaged DNA template:trimmed

nascent mRNA
R-HSA-6782138 (Reactome)
TC-NER pre-incision

complex:Partially open bubble damaged DNA template:trimmed

nascent mRNA
ArrowR-HSA-6782131 (Reactome)
TC-NER pre-incision

complex:Partially open bubble damaged DNA template:trimmed

nascent mRNA
R-HSA-9684118 (Reactome)
TC-NER pre-incision

complex:Partially open bubble damaged DNA template:trimmed

nascent mRNA
mim-catalysisR-HSA-9684118 (Reactome)
TC-NER pre-incision complexArrowR-HSA-6782069 (Reactome)
TC-NER pre-incision complexR-HSA-6782131 (Reactome)
TC-NER pre-incision complexmim-catalysisR-HSA-6782131 (Reactome)
TCEA1ArrowR-HSA-6782234 (Reactome)
TCEA1R-HSA-6782004 (Reactome)
TFIIH CoreArrowR-HSA-5690988 (Reactome)
TFIIHArrowR-HSA-6782234 (Reactome)
TFIIHR-HSA-5691000 (Reactome)
TFIIHR-HSA-6781818 (Reactome)
UBE2IArrowR-HSA-6790454 (Reactome)
UBE2N:UBE2V2ArrowR-HSA-6790487 (Reactome)
USP45mim-catalysisR-HSA-5696465 (Reactome)
UV-DDB:COP9 SignalosomeR-HSA-5691006 (Reactome)
UVSSA:USP7ArrowR-HSA-6782234 (Reactome)
UVSSA:USP7R-HSA-6782004 (Reactome)
Ub,SUMO,K63polyUb:XPC:RAD23:CETN2ArrowR-HSA-6790487 (Reactome)
Ub,SUMO:XPC:RAD23:CETN2:Open bubble-dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1, PAR-PARP2:CHD1LArrowR-HSA-6790454 (Reactome)
Ub,SUMO:XPC:RAD23:CETN2:Open bubble-dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1, PAR-PARP2:CHD1LR-HSA-6790487 (Reactome)
Ub:ERCC1R-HSA-5696465 (Reactome)
Ub:ERCC6ArrowR-HSA-6782234 (Reactome)
Ub:XPC:RAD23:CETN2:Distorted dsDNA:PAR-UV-DDB:PAR-PARP1,PAR-PARP2ArrowR-HSA-5696655 (Reactome)
Ub:XPC:RAD23:CETN2:Distorted dsDNA:PAR-UV-DDB:PAR-PARP1,PAR-PARP2R-HSA-5691000 (Reactome)
Ub:XPC:RAD23:CETN2:Distorted dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1,PAR-PARP2:CHD1LArrowR-HSA-5696670 (Reactome)
Ub:XPC:RAD23:CETN2:Distorted dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1,PAR-PARP2:CHD1LR-HSA-5690996 (Reactome)
Ub:XPC:RAD23:CETN2:Distorted dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1,PAR-PARP2:CHD1Lmim-catalysisR-HSA-5690996 (Reactome)
Ub:XPC:RAD23:CETN2:Distorted dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1,PAR-PARP2ArrowR-HSA-5689861 (Reactome)
Ub:XPC:RAD23:CETN2:Distorted dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1,PAR-PARP2R-HSA-5696670 (Reactome)
Ub:XPC:RAD23:CETN2:Distorted dsDNA:PAR-UV-DDB:TFIIH:PAR-PARP1,PAR-PARP2ArrowR-HSA-5691000 (Reactome)
Ub:XPC:RAD23:CETN2:Distorted dsDNA:PAR-UV-DDB:TFIIH:PAR-PARP1,PAR-PARP2R-HSA-5689861 (Reactome)
Ub:XPC:RAD23:CETN2:Distorted dsDNA:UV-DDB:PARP1,PARP2ArrowR-HSA-5696664 (Reactome)
Ub:XPC:RAD23:CETN2:Distorted dsDNA:UV-DDB:PARP1,PARP2R-HSA-5696655 (Reactome)
Ub:XPC:RAD23:CETN2:Distorted dsDNA:UV-DDBArrowR-HSA-6782943 (Reactome)
Ub:XPC:RAD23:CETN2:Distorted dsDNA:UV-DDBR-HSA-5696664 (Reactome)
Ub:XPC:RAD23:CETN2:Open bubble-dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1,PAR-PARP2:CHD1LArrowR-HSA-5690996 (Reactome)
Ub:XPC:RAD23:CETN2:Open bubble-dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1,PAR-PARP2:CHD1LR-HSA-6790454 (Reactome)
UbArrowR-HSA-5696465 (Reactome)
UbArrowR-HSA-6782069 (Reactome)
UbR-HSA-6781867 (Reactome)
UbR-HSA-6782943 (Reactome)
Ubiquitinated,hyperphosphorylated RNA Pol II:Damaged DNA template:nascent mRNA hybrid:TFIIH:Ub:ERCC6:ERCC8:DDB1:CUL4:RBX1:UVSSA:USP7:XAB2 complex:XPA:TCEA1:HMGN1:EP300ArrowR-HSA-6782004 (Reactome)
Ubiquitinated,hyperphosphorylated RNA Pol II:Damaged DNA template:nascent mRNA hybrid:TFIIH:Ub:ERCC6:ERCC8:DDB1:CUL4:RBX1:UVSSA:USP7:XAB2 complex:XPA:TCEA1:HMGN1:EP300R-HSA-6782069 (Reactome)
Ubiquitinated,hyperphosphorylated RNA Pol II:Damaged DNA template:nascent mRNA hybrid:TFIIH:Ub:ERCC6:ERCC8:DDB1:CUL4:RBX1:UVSSA:USP7:XAB2 complex:XPA:TCEA1:HMGN1:EP300mim-catalysisR-HSA-6782069 (Reactome)
Ubiquitinated,hyperphosphorylated RNA Pol II:Damaged DNA template:nascent mRNA hybrid:TFIIH:Ub:ERCC6:ERCC8:DDB1:CUL4:RBX1ArrowR-HSA-6781867 (Reactome)
Ubiquitinated,hyperphosphorylated RNA Pol II:Damaged DNA template:nascent mRNA hybrid:TFIIH:Ub:ERCC6:ERCC8:DDB1:CUL4:RBX1R-HSA-6782004 (Reactome)
XAB2 complexArrowR-HSA-6782234 (Reactome)
XAB2 complexR-HSA-6782004 (Reactome)
XPAArrowR-HSA-5690988 (Reactome)
XPAArrowR-HSA-6782224 (Reactome)
XPAR-HSA-5689861 (Reactome)
XPAR-HSA-6782004 (Reactome)
XPC:RAD23:CETN2:Distorted dsDNA:UV-DDBArrowR-HSA-5691006 (Reactome)
XPC:RAD23:CETN2:Distorted dsDNA:UV-DDBR-HSA-6782943 (Reactome)
XPC:RAD23:CETN2:Distorted dsDNA:UV-DDBmim-catalysisR-HSA-6782943 (Reactome)
XPC:RAD23:CETN2ArrowR-HSA-5691004 (Reactome)
XPC:RAD23:CETN2R-HSA-5691006 (Reactome)
XPCR-HSA-5691004 (Reactome)
dNTPR-HSA-5691001 (Reactome)
dNTPR-HSA-6782208 (Reactome)
dsDNAArrowR-HSA-5690997 (Reactome)
dsDNAArrowR-HSA-6782234 (Reactome)
excised DNA fragment with lesionArrowR-HSA-5690988 (Reactome)
mRNAArrowR-HSA-6782234 (Reactome)
ribonucleoside triphosphateR-HSA-6781824 (Reactome)
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