Nucleotide Excision Repair (Homo sapiens)

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1, 8, 924, 72255XPC:HR23B complex[nucleoplasm]XPC:HR23B complex[nucleoplasm]TFIIH [nucleoplasm]XPC:HR23B complex[nucleoplasm]Active Pol II transcriptioncomplex with damagedDNA hybrid[nucleoplasm]XPC:HR23B complex[nucleoplasm]XPC:HR23B complex[nucleoplasm]RNA Polymerase IIholoenzyme complex(hyperphosphorylated)[nucleoplasm]RPA heterotrimer[nucleoplasm]incision complex forGG-NER [nucleoplasm]XPC:HR23B:damagedDNA complex[nucleoplasm]Stalled Pol II inTC-NER [nucleoplasm]DNA Polymerase deltatetramer[nucleoplasm]RNA Polymerase IIholoenzyme complex(hyperphosphorylated)[nucleoplasm]RNA Polymerase IIholoenzyme complex(hyperphosphorylated)[nucleoplasm]TFIIH [nucleoplasm]RNA Polymerase IIholoenzyme complex(hyperphosphorylated)[nucleoplasm]Incision complex with 3'-inciseddamaged DNA[nucleoplasm]XPC:HR23B:damagedDNA complex[nucleoplasm]Active Pol IIcomplex withrepaired DNAtemplate:mRNA hybrid[nucleoplasm]RPA heterotrimer[nucleoplasm]pre-incision complexwith open DNA bubble [nucleoplasm]ERCC1:XPF complex[nucleoplasm]CAK [nucleoplasm]RPA heterotrimer[nucleoplasm]TFIIH [nucleoplasm]CAK [nucleoplasm]TFIIH [nucleoplasm]PCNA homotrimer[nucleoplasm]RPA heterotrimer[nucleoplasm]XPC:HR23B complex[nucleoplasm]DNA polymeraseepsilon[nucleoplasm]nucleoplasmTranscription-coupled(TC) repair complex[nucleoplasm]TFIIH [nucleoplasm]ERCC1:XPF complex[nucleoplasm]Stalled Pol IIcomplex with damagedDNA hybrid[nucleoplasm]CAK [nucleoplasm]DNA Polymerase deltatetramer[nucleoplasm]RPA heterotrimer[nucleoplasm]pre-incision complexin GG-NER[nucleoplasm]ERCC1:XPF complex[nucleoplasm]CAK [nucleoplasm]ERCC1:XPF complex[nucleoplasm]pre-incision complexwith open DNA bubble [nucleoplasm]RFC Heteropentamer[nucleoplasm]TFIIH [nucleoplasm]CAK [nucleoplasm]RNA Polymerase IIholoenzyme complex(hyperphosphorylated)[nucleoplasm]CAK [nucleoplasm]GTF2H4 [nucleoplasm]GTF2H1(2-548)[nucleoplasm]pre-incision complexwith open DNA bubblePOLR2L [nucleoplasm]ERCC3 [nucleoplasm]POLR2E [nucleoplasm]RPA2 [nucleoplasm]POLR2H [nucleoplasm]ERCC3 [nucleoplasm]RPA2 [nucleoplasm]POLD1 [nucleoplasm]POLR2C [nucleoplasm]POLR2D(2-142)[nucleoplasm]DNA Polymerase deltatetramerPCNA homotrimerIncision complex with 3'-inciseddamaged DNAPOLR2F(1-127)[nucleoplasm]POLD4 [nucleoplasm]dNTPPOLR2J [nucleoplasm]damaged DNAsubstratePOLR2C [nucleoplasm]ERCC5 [nucleoplasm]POLR2E [nucleoplasm]POLR2B [nucleoplasm]ERCC5 [nucleoplasm]POLR2D(2-142)[nucleoplasm]newly synthesizedDNA fragmentRAD23B [nucleoplasm]XPA(2-273)[nucleoplasm]XPC [nucleoplasm]ERCC4 [nucleoplasm]GTF2H2 [nucleoplasm]TCEA1POLR2J [nucleoplasm]RPA heterotrimerERCC3 [nucleoplasm]XPA(2-273)[nucleoplasm]ERCC2 [nucleoplasm]GTF2H1(2-548)[nucleoplasm]DDB2 [nucleoplasm]XPCRFC5 [nucleoplasm]POLR2H [nucleoplasm]CCNH [nucleoplasm]incised DNA withoutlesionCCNH [nucleoplasm]CCNH [nucleoplasm]ERCC4 [nucleoplasm]POLR2G [nucleoplasm]dNTPXAB2 [nucleoplasm]CCNH [nucleoplasm]GTF2H3 [nucleoplasm]p-S2,S5-POLR2A[nucleoplasm]DDB1dNTPERCC1 [nucleoplasm]CCNH [nucleoplasm]XPC:HR23B complexPOLR2K [nucleoplasm]RPA3 [nucleoplasm]CDK7 [nucleoplasm]RPA3 [nucleoplasm]p-S2,S5-POLR2A[nucleoplasm]POLE2 [nucleoplasm]GTF2H2 [nucleoplasm]GTF2H4 [nucleoplasm]XPC [nucleoplasm]POLR2C [nucleoplasm]GTF2H2 [nucleoplasm]ERCC2 [nucleoplasm]DDB1 [nucleoplasm]ERCC6 [nucleoplasm]POLR2I [nucleoplasm]DDB1 [nucleoplasm]GTF2H1(2-548)[nucleoplasm]POLR2B [nucleoplasm]POLR2K [nucleoplasm]ERCC1 [nucleoplasm]p-S2,S5-POLR2A[nucleoplasm]XAB2POLR2J [nucleoplasm]POLR2K [nucleoplasm]ERCC4 [nucleoplasm]repaired DNAtemplate:nascentmRNA hybriddamaged DNAsubstrate:nascentmRNA hybrid withdual incisionsPOLD1 [nucleoplasm]POLR2I [nucleoplasm]Transcription-coupled(TC) repair complexRPA1 [nucleoplasm]POLR2I [nucleoplasm]GTF2H1(2-548)[nucleoplasm]POLR2L [nucleoplasm]ERCC5RPA2 [nucleoplasm]RPA1 [nucleoplasm]POLR2F(1-127)[nucleoplasm]MNAT1 [nucleoplasm]newly synthesizedDNA fragmentPOLD3 [nucleoplasm]ERCC2 [nucleoplasm]RPA3 [nucleoplasm]GTF2H4 [nucleoplasm]GTF2H4 [nucleoplasm]XPC [nucleoplasm]RAD23B [nucleoplasm]newly synthesizedDNA fragmentMNAT1 [nucleoplasm]POLR2B [nucleoplasm]CDK7 [nucleoplasm]XPC [nucleoplasm]GTF2H1(2-548)[nucleoplasm]DNA Polymerase deltatetramerPOLR2C [nucleoplasm]RFC4 [nucleoplasm]ERCC2 [nucleoplasm]damaged DNAsubstrate:nascentmRNA hybridERCC5 [nucleoplasm]POLR2G [nucleoplasm]XPA(2-273)[nucleoplasm]POLR2G [nucleoplasm]Stalled Pol II inTC-NERERCC1 [nucleoplasm]POLR2C [nucleoplasm]ERCC1 [nucleoplasm]XPA(2-273)RFC HeteropentamerPOLD3 [nucleoplasm]RAD23B [nucleoplasm]GTF2H4 [nucleoplasm]CCNH [nucleoplasm]GTF2H2 [nucleoplasm]TFIIHnewly synthesizedDNA fragmentDDB2incision complex forGG-NERRPA3 [nucleoplasm]excised DNA fragmentwith lesionERCC5 [nucleoplasm]ERCC6p-S2,S5-POLR2A[nucleoplasm]POLR2F(1-127)[nucleoplasm]ERCC2 [nucleoplasm]RAD23B [nucleoplasm]newly synthesizedDNA fragmentRPA2 [nucleoplasm]RNA Polymerase IIholoenzyme complex(hyperphosphorylated)ERCC1GTF2H1(2-548)[nucleoplasm]incised DNA withoutlesionGTF2H2 [nucleoplasm]POLR2H [nucleoplasm]POLR2G [nucleoplasm]RPA1 [nucleoplasm]RPA2 [nucleoplasm]RAD23B [nucleoplasm]DNA polymeraseepsilonERCC5 [nucleoplasm]MNAT1 [nucleoplasm]POLR2E [nucleoplasm]DDB2 [nucleoplasm]ERCC2 [nucleoplasm]pre-incision complexin GG-NERRAD23B [nucleoplasm]XPC:HR23B:damagedDNA complexPOLR2H [nucleoplasm]DDB1 [nucleoplasm]DDB2 [nucleoplasm]POLR2I [nucleoplasm]dNTPPOLR2F(1-127)[nucleoplasm]ERCC4 [nucleoplasm]POLR2D(2-142)[nucleoplasm]POLR2D(2-142)[nucleoplasm]LIG1Stalled Pol IIcomplex with damagedDNA hybridERCC3 [nucleoplasm]RAD23BPOLR2E [nucleoplasm]RFC3 [nucleoplasm]POLD2 [nucleoplasm]damaged DNAsubstrate:nascentmRNA hybrid with 3'incisionPOLD4 [nucleoplasm]ERCC4RPA1 [nucleoplasm]RFC1 [nucleoplasm]POLR2F(1-127)[nucleoplasm]POLR2K [nucleoplasm]PCNA [nucleoplasm]POLR2H [nucleoplasm]DDB2 [nucleoplasm]POLR2J [nucleoplasm]DDB1 [nucleoplasm]ERCC8 [nucleoplasm]GTF2H2 [nucleoplasm]POLR2I [nucleoplasm]incised DNA withoutlesionActive Pol II transcriptioncomplex with damagedDNA hybridRPA3 [nucleoplasm]CDK7 [nucleoplasm]MNAT1 [nucleoplasm]POLR2L [nucleoplasm]Active Pol IIcomplex withrepaired DNAtemplate:mRNA hybridPOLR2E [nucleoplasm]Repaireddouble-stranded DNAnewly synthesizedDNA fragmentCDK7 [nucleoplasm]POLR2J [nucleoplasm]POLR2L [nucleoplasm]POLR2B [nucleoplasm]XPC [nucleoplasm]CDK7 [nucleoplasm]MNAT1 [nucleoplasm]POLR2L [nucleoplasm]ERCC8ERCC3 [nucleoplasm]POLR2B [nucleoplasm]TCEA1 [nucleoplasm]MNAT1 [nucleoplasm]RPA1 [nucleoplasm]POLR2D(2-142)[nucleoplasm]XPA(2-273)[nucleoplasm]XPC [nucleoplasm]POLD2 [nucleoplasm]POLR2K [nucleoplasm]p-S2,S5-POLR2A[nucleoplasm]GTF2H3 [nucleoplasm]ERCC3 [nucleoplasm]ERCC1:XPF complexGTF2H3 [nucleoplasm]POLR2G [nucleoplasm]RFC2 [nucleoplasm]CDK7 [nucleoplasm]GTF2H3 [nucleoplasm]incised DNA withoutlesionPOLE [nucleoplasm]GTF2H3 [nucleoplasm]GTF2H3 [nucleoplasm]GTF2H4 [nucleoplasm]333336


Description

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. These XP cells exhibited an ultraviolet radiation hypersensitivity leading to a hypermutability response to UV, offering a direct connection between deficient NER, increased mutations, and cancer. While the NER pathway in prokaryotes is unique, the pathway utilized in yeast and higher eukaryotes is highly conserved and includes a variety of proteins that interact to form complexes.
NER is involved in the repair of bulky adducts in DNA, such as UV-induced photo lesions [of both 6-4 photoproducts (6-4 pps) and cyclobutane pyrimidine dimer (CPDs)], intrastrand cross-links, large 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, excision of the oligonucleotide bearing the lesion, and accessory proteins necessary for efficient function. Polymerization and ligation restore the strand to its original state. NER consists of two related pathways called global genomic repair (GG-NER) and transcription-coupled NER (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 considered to be transcription-independent, removing lesions from non-transcribed regions of genome in addition to non-transcribed strands of transcribed regions. The preferential repair of UV-induced damage in transcribed strands of active genes is known as Transcription-coupled NER (TC-NER).
Several of the proteins involved in NER are key components of the basal transcription complex TFIIH. NER proteins have also been shown to interact with the 19S regulatory subunit of the proteasome, suggesting a role in cellular regulation signal pathways. The establishment of mutant mouse models for NER genes and other DNA repair-related genes have been useful in demonstrating the associations between NER defects and cancer.

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  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
Active Pol II

complex with repaired DNA

template:mRNA hybrid
ComplexREACT_2462 (Reactome)
Active Pol II

transcription complex with damaged

DNA hybrid
ComplexREACT_3609 (Reactome)
CCNH [nucleoplasm]ProteinP51946 (Uniprot-TrEMBL)
CDK7 [nucleoplasm]ProteinP50613 (Uniprot-TrEMBL)
DDB1 [nucleoplasm]ProteinQ16531 (Uniprot-TrEMBL)
DDB1ProteinQ16531 (Uniprot-TrEMBL)
DDB2 [nucleoplasm]ProteinQ92466 (Uniprot-TrEMBL)
DDB2ProteinQ92466 (Uniprot-TrEMBL)
DNA Polymerase delta tetramerComplexREACT_5801 (Reactome)
DNA polymerase epsilonComplexREACT_4621 (Reactome)
ERCC1 [nucleoplasm]ProteinP07992 (Uniprot-TrEMBL)
ERCC1:XPF complexComplexREACT_3454 (Reactome)
ERCC1ProteinP07992 (Uniprot-TrEMBL)
ERCC2 [nucleoplasm]ProteinP18074 (Uniprot-TrEMBL)
ERCC3 [nucleoplasm]ProteinP19447 (Uniprot-TrEMBL)
ERCC4 [nucleoplasm]ProteinQ92889 (Uniprot-TrEMBL)
ERCC4ProteinQ92889 (Uniprot-TrEMBL)
ERCC5 [nucleoplasm]ProteinP28715 (Uniprot-TrEMBL)
ERCC5ProteinP28715 (Uniprot-TrEMBL)
ERCC6 [nucleoplasm]ProteinQ03468 (Uniprot-TrEMBL)
ERCC6ProteinQ03468 (Uniprot-TrEMBL)
ERCC8 [nucleoplasm]ProteinQ13216 (Uniprot-TrEMBL)
ERCC8ProteinQ13216 (Uniprot-TrEMBL)
GTF2H1(2-548) [nucleoplasm]ProteinP32780 (Uniprot-TrEMBL)
GTF2H2 [nucleoplasm]ProteinQ13888 (Uniprot-TrEMBL)
GTF2H3 [nucleoplasm]ProteinQ13889 (Uniprot-TrEMBL)
GTF2H4 [nucleoplasm]ProteinQ92759 (Uniprot-TrEMBL)
Incision complex

with 3'-incised

damaged DNA
ComplexREACT_5099 (Reactome)
LIG1ProteinP18858 (Uniprot-TrEMBL)
MNAT1 [nucleoplasm]ProteinP51948 (Uniprot-TrEMBL)
PCNA [nucleoplasm]ProteinP12004 (Uniprot-TrEMBL)
PCNA homotrimerComplexREACT_2542 (Reactome)
POLD1 [nucleoplasm]ProteinP28340 (Uniprot-TrEMBL)
POLD2 [nucleoplasm]ProteinP49005 (Uniprot-TrEMBL)
POLD3 [nucleoplasm]ProteinQ15054 (Uniprot-TrEMBL)
POLD4 [nucleoplasm]ProteinQ9HCU8 (Uniprot-TrEMBL)
POLE [nucleoplasm]ProteinQ07864 (Uniprot-TrEMBL)
POLE2 [nucleoplasm]ProteinP56282 (Uniprot-TrEMBL)
POLR2B [nucleoplasm]ProteinP30876 (Uniprot-TrEMBL)
POLR2C [nucleoplasm]ProteinP19387 (Uniprot-TrEMBL)
POLR2D(2-142) [nucleoplasm]ProteinO15514 (Uniprot-TrEMBL)
POLR2E [nucleoplasm]ProteinP19388 (Uniprot-TrEMBL)
POLR2F(1-127) [nucleoplasm]ProteinP61218 (Uniprot-TrEMBL)
POLR2G [nucleoplasm]ProteinP62487 (Uniprot-TrEMBL)
POLR2H [nucleoplasm]ProteinP52434 (Uniprot-TrEMBL)
POLR2I [nucleoplasm]ProteinP36954 (Uniprot-TrEMBL)
POLR2J [nucleoplasm]ProteinP52435 (Uniprot-TrEMBL)
POLR2K [nucleoplasm]ProteinP53803 (Uniprot-TrEMBL)
POLR2L [nucleoplasm]ProteinP62875 (Uniprot-TrEMBL)
RAD23B [nucleoplasm]ProteinP54727 (Uniprot-TrEMBL)
RAD23BProteinP54727 (Uniprot-TrEMBL)
RFC HeteropentamerComplexREACT_4881 (Reactome)
RFC1 [nucleoplasm]ProteinP35251 (Uniprot-TrEMBL)
RFC2 [nucleoplasm]ProteinP35250 (Uniprot-TrEMBL)
RFC3 [nucleoplasm]ProteinP40938 (Uniprot-TrEMBL)
RFC4 [nucleoplasm]ProteinP35249 (Uniprot-TrEMBL)
RFC5 [nucleoplasm]ProteinP40937 (Uniprot-TrEMBL)
RNA Polymerase II

holoenzyme complex

(hyperphosphorylated)
ComplexREACT_4889 (Reactome)
RPA heterotrimerComplexREACT_3427 (Reactome)
RPA1 [nucleoplasm]ProteinP27694 (Uniprot-TrEMBL)
RPA2 [nucleoplasm]ProteinP15927 (Uniprot-TrEMBL)
RPA3 [nucleoplasm]ProteinP35244 (Uniprot-TrEMBL)
Repaired double-stranded DNAREACT_4318 (Reactome)
Stalled Pol II

complex with damaged

DNA hybrid
ComplexREACT_3072 (Reactome)
Stalled Pol II in TC-NERComplexREACT_4443 (Reactome)
TCEA1 [nucleoplasm]ProteinP23193 (Uniprot-TrEMBL)
TCEA1ProteinP23193 (Uniprot-TrEMBL)
TFIIHComplexREACT_3832 (Reactome)
Transcription-coupled (TC) repair complexComplexREACT_3969 (Reactome)
XAB2 [nucleoplasm]ProteinQ9HCS7 (Uniprot-TrEMBL)
XAB2ProteinQ9HCS7 (Uniprot-TrEMBL)
XPA(2-273) [nucleoplasm]ProteinP23025 (Uniprot-TrEMBL)
XPA(2-273)ProteinP23025 (Uniprot-TrEMBL)
XPC [nucleoplasm]ProteinQ01831 (Uniprot-TrEMBL)
XPC:HR23B complexComplexREACT_4017 (Reactome)
XPC:HR23B:damaged DNA complexComplexREACT_3245 (Reactome)
XPCProteinQ01831 (Uniprot-TrEMBL)
dNTPREACT_2960 (Reactome)
damaged DNA

substrate:nascent mRNA hybrid with

dual incisions
REACT_5428 (Reactome)
damaged DNA

substrate:nascent mRNA hybrid with 3'

incision
REACT_2845 (Reactome)
damaged DNA

substrate:nascent

mRNA hybrid
REACT_3022 (Reactome)
damaged DNA substrateREACT_2765 (Reactome)
excised DNA fragment with lesionREACT_2556 (Reactome)
incised DNA without lesionREACT_3852 (Reactome)
incision complex for GG-NERComplexREACT_5159 (Reactome)
newly synthesized DNA fragmentREACT_3448 (Reactome)
p-S2,S5-POLR2A [nucleoplasm]ProteinP24928 (Uniprot-TrEMBL)
pre-incision complex in GG-NERComplexREACT_5795 (Reactome)
pre-incision complex with open DNA bubbleComplexREACT_5689 (Reactome)
repaired DNA

template:nascent

mRNA hybrid
REACT_5433 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
Active Pol II

complex with repaired DNA

template:mRNA hybrid
ArrowREACT_551 (Reactome)
Active Pol II

transcription complex with damaged

DNA hybrid
ArrowREACT_1453 (Reactome)
Active Pol II

transcription complex with damaged

DNA hybrid
REACT_1947 (Reactome)
DDB1ArrowREACT_1311 (Reactome)
DDB1REACT_1492 (Reactome)
DDB2ArrowREACT_1311 (Reactome)
DDB2REACT_1492 (Reactome)
DNA Polymerase delta tetramerArrowREACT_1196 (Reactome)
DNA Polymerase delta tetramerArrowREACT_465 (Reactome)
DNA Polymerase delta tetramerREACT_1196 (Reactome)
DNA Polymerase delta tetramerREACT_465 (Reactome)
DNA Polymerase delta tetramermim-catalysisREACT_1196 (Reactome)
DNA Polymerase delta tetramermim-catalysisREACT_465 (Reactome)
DNA polymerase epsilonArrowREACT_353 (Reactome)
DNA polymerase epsilonArrowREACT_677 (Reactome)
DNA polymerase epsilonREACT_353 (Reactome)
DNA polymerase epsilonREACT_677 (Reactome)
DNA polymerase epsilonmim-catalysisREACT_353 (Reactome)
DNA polymerase epsilonmim-catalysisREACT_677 (Reactome)
ERCC1:XPF complexArrowREACT_1311 (Reactome)
ERCC1:XPF complexArrowREACT_1438 (Reactome)
ERCC1:XPF complexREACT_1584 (Reactome)
ERCC1:XPF complexREACT_2163 (Reactome)
ERCC1REACT_1438 (Reactome)
ERCC4REACT_1438 (Reactome)
ERCC5ArrowREACT_1311 (Reactome)
ERCC5REACT_1492 (Reactome)
ERCC5REACT_1584 (Reactome)
ERCC6REACT_1584 (Reactome)
ERCC8REACT_1584 (Reactome)
Incision complex

with 3'-incised

damaged DNA
ArrowREACT_1124 (Reactome)
Incision complex

with 3'-incised

damaged DNA
REACT_1311 (Reactome)
Incision complex

with 3'-incised

damaged DNA
mim-catalysisREACT_1311 (Reactome)
LIG1ArrowREACT_2181 (Reactome)
LIG1ArrowREACT_527 (Reactome)
LIG1REACT_2181 (Reactome)
LIG1REACT_527 (Reactome)
LIG1mim-catalysisREACT_2181 (Reactome)
LIG1mim-catalysisREACT_527 (Reactome)
PCNA homotrimerArrowREACT_1196 (Reactome)
PCNA homotrimerArrowREACT_353 (Reactome)
PCNA homotrimerArrowREACT_465 (Reactome)
PCNA homotrimerArrowREACT_677 (Reactome)
PCNA homotrimerREACT_1196 (Reactome)
PCNA homotrimerREACT_353 (Reactome)
PCNA homotrimerREACT_465 (Reactome)
PCNA homotrimerREACT_677 (Reactome)
RAD23BREACT_1984 (Reactome)
REACT_1033 (Reactome) Two DNA helicases XPG and XPD, which are part of TFIIH, unwind DNA duplex around this lesion to form an open bubble structure that exposes the damaged site.

REACT_1124 (Reactome) The cleavage of the damaged strand of DNA 3' 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 incision is carried out by XPG.

REACT_1196 (Reactome) At the beginning of this reaction, 1 molecule of 'dNTP', 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', 1 molecule of 'DNA Polymerase delta tetramer', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with dual incisions' are present. At the end of this reaction, 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', 1 molecule of 'newly synthesized DNA fragment ', 1 molecule of 'DNA Polymerase delta tetramer', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with dual incisions' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'delta DNA polymerase activity' of 'DNA Polymerase delta tetramer'.

REACT_1274 (Reactome) At the beginning of this reaction, 1 molecule of 'Transcription-coupled (TC) repair complex', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid' are present. At the end of this reaction, 1 molecule of 'Transcription-coupled (TC) repair complex', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with 3' incision' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'endodeoxyribonuclease activity' of 'Transcription-coupled (TC) repair complex'.

REACT_1284 (Reactome) At the beginning of this reaction, 1 molecule of 'Transcription-coupled (TC) repair complex', and 1 molecule of 'Stalled Pol II complex with damaged DNA hybrid' are present. At the end of this reaction, 1 molecule of 'Transcription-coupled (TC) repair complex', 1 molecule of 'Stalled Pol II in TC-NER', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid' are present.

This reaction takes place in the 'nucleus'.

REACT_1311 (Reactome) 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 incision is carried out by ERCC1-XPF complex.

REACT_1438 (Reactome) At the beginning of this reaction, 1 molecule of 'ERCC1, DNA excision repair protein', and 1 molecule of 'XPF protein' are present. At the end of this reaction, 1 molecule of 'ERCC1:XPF complex' is present.

This reaction takes place in the 'nucleus'.

REACT_1453 (Reactome) An active Pol II complex consisting mainly of the Pol II holoenzyme transcribes the damaged DNA template.

REACT_1492 (Reactome) Transcription factor II H (TFIIH) and XPG are added to the damaged site on the DNA to form a pre-incision complex along with lesioned DNA template.

REACT_1584 (Reactome) A proper assembly of repair complex may require displacement of Pol II from the damage site exposing a significant length of the corresponding template DNA with the lesions. Speculations on the mode of this displacement of Pol II are available from experimental evidences: a. CSB mediated dissociation of Pol II b. degradation of Pol II c. CSB mediated remodeling of damaged DNA-RNA PII interface etc.
The TC-repair complex now consists of damaged DNA template: nascent mRNA hybrid. The damage site needs to be exposed to subsequent endonuclease activities.

REACT_1947 (Reactome) At the site of damage, the Pol II complex is arrested resulting in reduced levels of transcription. Several models have been proposed to explain the mechanism of this transcriptional downregulation. These include a. hyperphosphorylation of Pol II resulting in aborted entry to new pre-initiation complexes b. sequestration of TATA-binding proteins (TBP) c. enhanced use of TFIIH complexes for repair purposes precluding their use in transcription.

REACT_1984 (Reactome) XPC is mutated in individuals with xeroderma pigmentosum from genetic Complementation Group C (XP-C). It forms a tight heterodimeric complex with human Rad 23B homolog, HR23B and is thought to bind to the damaged site with lesion first triggering subsequent reactions

REACT_1987 (Reactome) Disruption of normal Watson-Crick base pairing and altered chemistry in the damaged strand involving bases may act as signals of damage that are recognized by XPC:HR23B complex.

REACT_2163 (Reactome) ERCC1-XPF complex with 5’ endonuclease activity binds to this pre-incision complex around the bubble structure to form an active incision complex.

REACT_2181 (Reactome) DNA Ligase 1 ligates the newly synthesized fragment to the gap in the template DNA.

REACT_353 (Reactome) At the beginning of this reaction, 1 molecule of 'dNTP', 1 molecule of 'incised DNA without lesion', 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', and 1 molecule of 'DNA polymerase epsilon' are present. At the end of this reaction, 1 molecule of 'incised DNA without lesion', 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', 1 molecule of 'newly synthesized DNA fragment ', and 1 molecule of 'DNA polymerase epsilon' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'DNA-directed DNA polymerase activity' of 'DNA polymerase epsilon'.

REACT_465 (Reactome) At the beginning of this reaction, 1 molecule of 'dNTP', 1 molecule of 'incised DNA without lesion', 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', and 1 molecule of 'DNA Polymerase delta tetramer' are present. At the end of this reaction, 1 molecule of 'incised DNA without lesion', 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', 1 molecule of 'newly synthesized DNA fragment ', and 1 molecule of 'DNA Polymerase delta tetramer' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'delta DNA polymerase activity' of 'DNA Polymerase delta tetramer'.

REACT_527 (Reactome) At the beginning of this reaction, 1 molecule of 'newly synthesized DNA fragment ', 1 molecule of 'DNA ligase I ', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with dual incisions' are present. At the end of this reaction, 1 molecule of 'repaired DNA template:nascent mRNA hybrid', and 1 molecule of 'DNA ligase I ' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'DNA ligase activity' of 'DNA ligase I '.

REACT_551 (Reactome) At the beginning of this reaction, 1 molecule of 'Stalled Pol II in TC-NER', and 1 molecule of 'repaired DNA template:nascent mRNA hybrid' are present. At the end of this reaction, 1 molecule of 'Active Pol II complex with repaired DNA template:mRNA hybrid' is present.

This reaction takes place in the 'nucleus'.

REACT_677 (Reactome) At the beginning of this reaction, 1 molecule of 'dNTP', 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', 1 molecule of 'DNA polymerase epsilon', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with dual incisions' are present. At the end of this reaction, 1 molecule of 'RPA heterotrimer', 1 molecule of 'PCNA homotrimer', 1 molecule of 'RFC Heteropentamer', 1 molecule of 'newly synthesized DNA fragment ', 1 molecule of 'DNA polymerase epsilon', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with dual incisions' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'DNA-directed DNA polymerase activity' of 'DNA polymerase epsilon'.

REACT_811 (Reactome) At the beginning of this reaction, 1 molecule of 'Transcription-coupled (TC) repair complex', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with 3' incision' are present. At the end of this reaction, 1 molecule of 'Transcription-coupled (TC) repair complex', 1 molecule of 'excised DNA fragment with lesion', and 1 molecule of 'damaged DNA substrate:nascent mRNA hybrid with dual incisions' are present.

This reaction takes place in the 'nucleus' and is mediated by the 'endodeoxyribonuclease activity' of 'Transcription-coupled (TC) repair complex'.

RFC HeteropentamerArrowREACT_1196 (Reactome)
RFC HeteropentamerArrowREACT_353 (Reactome)
RFC HeteropentamerArrowREACT_465 (Reactome)
RFC HeteropentamerArrowREACT_677 (Reactome)
RFC HeteropentamerREACT_1196 (Reactome)
RFC HeteropentamerREACT_353 (Reactome)
RFC HeteropentamerREACT_465 (Reactome)
RFC HeteropentamerREACT_677 (Reactome)
RNA Polymerase II

holoenzyme complex

(hyperphosphorylated)
REACT_1453 (Reactome)
RPA heterotrimerArrowREACT_1196 (Reactome)
RPA heterotrimerArrowREACT_1311 (Reactome)
RPA heterotrimerArrowREACT_353 (Reactome)
RPA heterotrimerArrowREACT_465 (Reactome)
RPA heterotrimerArrowREACT_677 (Reactome)
RPA heterotrimerREACT_1196 (Reactome)
RPA heterotrimerREACT_1492 (Reactome)
RPA heterotrimerREACT_353 (Reactome)
RPA heterotrimerREACT_465 (Reactome)
RPA heterotrimerREACT_677 (Reactome)
Repaired double-stranded DNAArrowREACT_2181 (Reactome)
Stalled Pol II

complex with damaged

DNA hybrid
ArrowREACT_1584 (Reactome)
Stalled Pol II

complex with damaged

DNA hybrid
ArrowREACT_1947 (Reactome)
Stalled Pol II

complex with damaged

DNA hybrid
REACT_1284 (Reactome)
Stalled Pol II

complex with damaged

DNA hybrid
REACT_1584 (Reactome)
Stalled Pol II in TC-NERArrowREACT_1284 (Reactome)
Stalled Pol II in TC-NERREACT_551 (Reactome)
TCEA1REACT_1584 (Reactome)
TFIIHArrowREACT_1311 (Reactome)
TFIIHREACT_1492 (Reactome)
TFIIHREACT_1584 (Reactome)
Transcription-coupled (TC) repair complexArrowREACT_1274 (Reactome)
Transcription-coupled (TC) repair complexArrowREACT_1284 (Reactome)
Transcription-coupled (TC) repair complexArrowREACT_1584 (Reactome)
Transcription-coupled (TC) repair complexArrowREACT_811 (Reactome)
Transcription-coupled (TC) repair complexREACT_1274 (Reactome)
Transcription-coupled (TC) repair complexREACT_1284 (Reactome)
Transcription-coupled (TC) repair complexREACT_811 (Reactome)
Transcription-coupled (TC) repair complexmim-catalysisREACT_1274 (Reactome)
Transcription-coupled (TC) repair complexmim-catalysisREACT_811 (Reactome)
XAB2REACT_1584 (Reactome)
XPA(2-273)ArrowREACT_1311 (Reactome)
XPA(2-273)REACT_1492 (Reactome)
XPC:HR23B complexArrowREACT_1311 (Reactome)
XPC:HR23B complexArrowREACT_1984 (Reactome)
XPC:HR23B complexREACT_1987 (Reactome)
XPC:HR23B:damaged DNA complexArrowREACT_1987 (Reactome)
XPC:HR23B:damaged DNA complexREACT_1492 (Reactome)
XPCREACT_1984 (Reactome)
dNTPREACT_1196 (Reactome)
dNTPREACT_353 (Reactome)
dNTPREACT_465 (Reactome)
dNTPREACT_677 (Reactome)
damaged DNA

substrate:nascent mRNA hybrid with

dual incisions
ArrowREACT_1196 (Reactome)
damaged DNA

substrate:nascent mRNA hybrid with

dual incisions
ArrowREACT_677 (Reactome)
damaged DNA

substrate:nascent mRNA hybrid with

dual incisions
ArrowREACT_811 (Reactome)
damaged DNA

substrate:nascent mRNA hybrid with

dual incisions
REACT_1196 (Reactome)
damaged DNA

substrate:nascent mRNA hybrid with

dual incisions
REACT_527 (Reactome)
damaged DNA

substrate:nascent mRNA hybrid with

dual incisions
REACT_677 (Reactome)
damaged DNA

substrate:nascent mRNA hybrid with 3'

incision
ArrowREACT_1274 (Reactome)
damaged DNA

substrate:nascent mRNA hybrid with 3'

incision
REACT_811 (Reactome)
damaged DNA

substrate:nascent

mRNA hybrid
ArrowREACT_1284 (Reactome)
damaged DNA

substrate:nascent

mRNA hybrid
REACT_1274 (Reactome)
damaged DNA

substrate:nascent

mRNA hybrid
REACT_1453 (Reactome)
damaged DNA substrateREACT_1987 (Reactome)
excised DNA fragment with lesionArrowREACT_1311 (Reactome)
excised DNA fragment with lesionArrowREACT_811 (Reactome)
incised DNA without lesionArrowREACT_1311 (Reactome)
incised DNA without lesionArrowREACT_353 (Reactome)
incised DNA without lesionArrowREACT_465 (Reactome)
incised DNA without lesionREACT_2181 (Reactome)
incised DNA without lesionREACT_353 (Reactome)
incised DNA without lesionREACT_465 (Reactome)
incision complex for GG-NERArrowREACT_2163 (Reactome)
incision complex for GG-NERREACT_1124 (Reactome)
incision complex for GG-NERmim-catalysisREACT_1124 (Reactome)
newly synthesized DNA fragmentArrowREACT_1196 (Reactome)
newly synthesized DNA fragmentArrowREACT_353 (Reactome)
newly synthesized DNA fragmentArrowREACT_465 (Reactome)
newly synthesized DNA fragmentArrowREACT_677 (Reactome)
newly synthesized DNA fragmentREACT_2181 (Reactome)
newly synthesized DNA fragmentREACT_527 (Reactome)
pre-incision complex in GG-NERArrowREACT_1492 (Reactome)
pre-incision complex in GG-NERREACT_1033 (Reactome)
pre-incision complex in GG-NERmim-catalysisREACT_1033 (Reactome)
pre-incision complex with open DNA bubbleArrowREACT_1033 (Reactome)
pre-incision complex with open DNA bubbleREACT_2163 (Reactome)
repaired DNA

template:nascent

mRNA hybrid
ArrowREACT_527 (Reactome)
repaired DNA

template:nascent

mRNA hybrid
REACT_551 (Reactome)
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