Nucleotide excision repair in xeroderma pigmentosum (Homo sapiens)

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2913014, 161235, 25447915179157RPAThe choice of DNA ligase depends on the DNA polymerase involved in repair synthesis and probably the stage of the cell cycle (Moser et al. 2007).Transcription factor II H (TFIIH)DNA lesionTranscription-coupled repairXPC complexUVRInhibition of UV-DDB when no UV-damage is present.With UV damage, inhibition is lifted UV-damaged DNA DNA polymerasesEarly chromatin remodelingStep 4 - Gap-filling, DNA synthesis and ligationTCR-initiation complexLegend:UV - RadiationDNAMutated XP geneNucleotide lesionStimulation UbiquitylationDNA damage signalingDNA unwinding by XPB and XPD helicasesUV-DDBorStep 1 - Recognition of damaged DNA20279SLX4BRCA1TFIISERCC6ERCC6 (CSB)XPATTDA/GTF2H5XRCC1RPA2RPA1POLKPOLD1PARP1XAB2Histone H2Ap52/GTF2H4RNA polymerase IIHistone H3CSN (COP9)HMGN1XPARPA3USP7XRCC1UVSSASLX4IPRAD18LIG3CHD1L (ALC1)BRCA1POLHRAD23BLIG1Histone H47262711122822482410, 13, 146, 10RBX1CUL4ACUL4BERCC8 (CSA)DDB1CDK7 MNAT1CCNHXPD/ERCC2XPB/ERCC3p62/GTF2H1p44/GTF2H2p34 /GTF2H3XPF/ERCC1XPG/ERCC43Step 3 - Incision and excisionPOLD2POLD3POLD4POLEPOLE2POLE3POLE4PCNARFC1RFC2RFC3RFC4RFC5LigationGlobal genome repairXPE complexRBX1CUL4A19CUL4BXPE (DDB2)DDB114XPCRAD23ACETN218RPARPA3RPA2RPA1In non-replicating cellsIn replicating cellsCSN (COP9)27XPD/ERCC2XPB/ERCC3RPARPA3RPA2RPA117Step 2 - DNA binding and unwinding


Description

Nucleotide excision repair is a DNA repair mechanism that repairs DNA damaged by UV radiation.

This type of damage produces bulky distortions in the shape of DNA double helix due to the addition of DNA adducts, mostly thymine dimers and 6,4-photoproducts.

Recognition of distortions leads to the removal of a short single-stranded DNA segment that includes the lesion, creating a single-strand gap in the DNA, which is subsequently filled in by DNA polymerase, which uses the undamaged strand as a template. NER can be divided into two subpathways (Global genomic NER and Transcription coupled NER) that differ only in their recognition of helix-distorting DNA damage. Nucleotide excision repair has more complexity in eukaryotes.

Nucleotide excision repair (NER) is a particularly important DNA repair mechanism as evidenced by the severe human diseases that result from in-born genetic mutations of NER proteins including Xeroderma pigmentosum and Cockayne's syndrome.

This pathway was adapted from KEGG, REPAIRtoire and Wikipedia. The pathway layout is based on KEGG.

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Bibliography

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  1. Graf N, Ang WH, Zhu G, Myint M, Lippard SJ; ''''; , PubMed Europe PMC Scholia
  2. 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.''; J Cell Biol, 2012 PubMed Europe PMC Scholia
  3. Renaud E, Miccoli L, Zacal N, Biard DS, Craescu CT, Rainbow AJ, Angulo JF; ''Differential contribution of XPC, RAD23A, RAD23B and CENTRIN 2 to the UV-response in human cells.''; DNA Repair (Amst), 2011 PubMed Europe PMC Scholia
  4. 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.''; Cell, 2011 PubMed Europe PMC Scholia
  5. Vasquez KM, Christensen J, Li L, Finch RA, Glazer PM; ''Human XPA and RPA DNA repair proteins participate in specific recognition of triplex-induced helical distortions.''; Proc Natl Acad Sci U S A, 2002 PubMed Europe PMC Scholia
  6. Zhang H, Chen Z, Ye Y, Ye Z, Cao D, Xiong Y, Srivastava M, Feng X, Tang M, Wang C, Tainer JA, Chen J; ''SLX4IP acts with SLX4 and XPF-ERCC1 to promote interstrand crosslink repair.''; Nucleic Acids Res, 2019 PubMed Europe PMC Scholia
  7. Miao F, Bouziane M, Dammann R, Masutani C, Hanaoka F, Pfeifer G, O'Connor TR; ''3-Methyladenine-DNA glycosylase (MPG protein) interacts with human RAD23 proteins.''; J Biol Chem, 2000 PubMed Europe PMC Scholia
  8. Rapić-Otrin V, McLenigan MP, Bisi DC, Gonzalez M, Levine AS; ''Sequential binding of UV DNA damage binding factor and degradation of the p48 subunit as early events after UV irradiation.''; Nucleic Acids Res, 2002 PubMed Europe PMC Scholia
  9. Zhang ET, He Y, Grob P, Fong YW, Nogales E, Tjian R; ''Architecture of the human XPC DNA repair and stem cell coactivator complex.''; Proc Natl Acad Sci U S A, 2015 PubMed Europe PMC Scholia
  10. 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.''; Mol Cell Biol, 2010 PubMed Europe PMC Scholia
  11. 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.''; Proc Natl Acad Sci U S A, 2006 PubMed Europe PMC Scholia
  12. 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.''; EMBO J, 2008 PubMed Europe PMC Scholia
  13. Thakar T, Leung W, Nicolae CM, Clements KE, Shen B, Bielinsky AK, Moldovan GL; ''Ubiquitinated-PCNA protects replication forks from DNA2-mediated degradation by regulating Okazaki fragment maturation and chromatin assembly.''; Nat Commun, 2020 PubMed Europe PMC Scholia
  14. Luijsterburg MS, Lindh M, Acs K, Vrouwe MG, Pines A, van Attikum H, Mullenders LH, Dantuma NP; ''DDB2 promotes chromatin decondensation at UV-induced DNA damage.''; J Cell Biol, 2012 PubMed Europe PMC Scholia
  15. Majka J, Burgers PM; ''The PCNA-RFC families of DNA clamps and clamp loaders.''; Prog Nucleic Acid Res Mol Biol, 2004 PubMed Europe PMC Scholia
  16. Kumar N, Raja S, Van Houten B; ''The involvement of nucleotide excision repair proteins in the removal of oxidative DNA damage.''; Nucleic Acids Res, 2020 PubMed Europe PMC Scholia
  17. Vermeulen W, Fousteri M; ''Mammalian transcription-coupled excision repair.''; Cold Spring Harb Perspect Biol, 2013 PubMed Europe PMC Scholia
  18. 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.''; Genes Dev, 2006 PubMed Europe PMC Scholia
  19. Liu L, Yin Y, Li Y, Prevedel L, Lacy EH, Ma L, Zhou P; ''Essential role of the CUL4B ubiquitin ligase in extra-embryonic tissue development during mouse embryogenesis.''; Cell Res, 2012 PubMed Europe PMC Scholia
  20. Sugasawa K, Okuda Y, Saijo M, Nishi R, Matsuda N, Chu G, Mori T, Iwai S, Tanaka K, Hanaoka F; ''UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex.''; Cell, 2005 PubMed Europe PMC Scholia
  21. Fadda E; ''Role of the XPA protein in the NER pathway: A perspective on the function of structural disorder in macromolecular assembly.''; Comput Struct Biotechnol J, 2016 PubMed Europe PMC Scholia
  22. 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.''; Mol Cell, 2007 PubMed Europe PMC Scholia
  23. Okuda M, Nakazawa Y, Guo C, Ogi T, Nishimura Y; ''Common TFIIH recruitment mechanism in global genome and transcription-coupled repair subpathways.''; Nucleic Acids Res, 2017 PubMed Europe PMC Scholia
  24. Zlatanou A, Despras E, Braz-Petta T, Boubakour-Azzouz I, Pouvelle C, Stewart GS, Nakajima S, Yasui A, Ishchenko AA, Kannouche PL; ''The hMsh2-hMsh6 complex acts in concert with monoubiquitinated PCNA and Pol η in response to oxidative DNA damage in human cells.''; Mol Cell, 2011 PubMed Europe PMC Scholia
  25. Huttner D, Ulrich HD; ''Cooperation of replication protein A with the ubiquitin ligase Rad18 in DNA damage bypass.''; Cell Cycle, 2008 PubMed Europe PMC Scholia
  26. 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.''; Mol Cell, 2010 PubMed Europe PMC Scholia
  27. Lee J, Zhou P; ''DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase.''; Mol Cell, 2007 PubMed Europe PMC Scholia
  28. Menoni H, Wienholz F, Theil AF, Janssens RC, Lans H, Campalans A, Radicella JP, Marteijn JA, Vermeulen W; ''The transcription-coupled DNA repair-initiating protein CSB promotes XRCC1 recruitment to oxidative DNA damage.''; Nucleic Acids Res, 2018 PubMed Europe PMC Scholia
  29. Borszéková Pulzová L, Ward TA, Chovanec M; ''XPA: DNA Repair Protein of Significant Clinical Importance.''; Int J Mol Sci, 2020 PubMed Europe PMC Scholia
  30. Tian F, Sharma S, Zou J, Lin SY, Wang B, Rezvani K, Wang H, Parvin JD, Ludwig T, Canman CE, Zhang D; ''BRCA1 promotes the ubiquitination of PCNA and recruitment of translesion polymerases in response to replication blockade.''; Proc Natl Acad Sci U S A, 2013 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
135241view22:54, 8 August 2024EweitzClear cache to update board dimensions
135240view22:53, 8 August 2024EweitzRefine case, paragraph positioning
135239view22:46, 8 August 2024EweitzEconomize layout
134573view23:31, 22 July 2024EweitzOntology Term : 'Cockayne syndrome' added !
134572view23:31, 22 July 2024EweitzModified description
134492view05:25, 22 July 2024EgonwRemoved template comments
134133view13:30, 30 June 2024EgonwConverted a label to a pathway datanode
119169view16:21, 19 June 2021NataliehCorrected a mistake
119168view16:20, 19 June 2021NataliehDeleted an unwanted node
119167view16:19, 19 June 2021NataliehMarked XP mutations
119166view15:53, 19 June 2021NataliehAdded missing links between some nodes
118858view12:07, 2 June 2021NataliehDeleted an unwanted node
118855view11:34, 2 June 2021FehrhartOntology Term : 'xeroderma pigmentosum' added !
118854view11:33, 2 June 2021FehrhartModified title
118781view16:50, 1 June 2021NataliehModified title
118767view15:30, 1 June 2021Natalieh
118766view15:30, 1 June 2021Natalieh
118765view15:25, 1 June 2021NataliehNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
BRCA1GeneProductBRCA1 (HGNC)
BRCA1GeneProductENSG00000012048 (Ensembl)
CCNHGeneProductENSG00000134480 (Ensembl)
CDK7 GeneProductENSG00000134058 (Ensembl) This subcomplex dissociates after XPA binds
CETN2GeneProductENSG00000147400 (Ensembl) "CENTRIN 2 enhances the affinity of XPC/RAD23B for DNA distortions"
CHD1L (ALC1)GeneProductENSG00000131778 (Ensembl)
CSN (COP9)ProteinA0A096LP07 (Uniprot-TrEMBL)
CUL4AGeneProductENSG00000139842 (Ensembl)
CUL4BGeneProductENSG00000158290 (Ensembl)
DDB1GeneProductENSG00000167986 (Ensembl)
ERCC6 (CSB) GeneProductENSG00000225830 (Ensembl) https://reactome.org/PathwayBrowser/#/R-HSA-5696398&SEL=R-HSA-6781823&PATH=R-HSA-73894
ERCC6GeneProductENSG00000225830 (Ensembl)
ERCC8 (CSA)GeneProductENSG00000049167 (Ensembl)
HMGN1GeneProductENSG00000205581 (Ensembl)
Histone H2AProteinA0A024R017 (Uniprot-TrEMBL)
Histone H3ProteinB2R4P9 (Uniprot-TrEMBL)
Histone H4ProteinB2R4R0 (Uniprot-TrEMBL)
LIG1GeneProductENSG00000105486 (Ensembl)
LIG3GeneProductENSG00000005156 (Ensembl)
MNAT1GeneProductENSG00000020426 (Ensembl)
PARP1GeneProductPARP1 (HGNC)
PCNAGeneProductENSG00000132646 (Ensembl)
POLD1GeneProductENSG00000062822 (Ensembl)
POLD2GeneProductENSG00000106628 (Ensembl)
POLD3GeneProductENSG00000077514 (Ensembl) DNA polymerase delta
POLD4GeneProductENSG00000175482 (Ensembl)
POLE2GeneProductENSG00000100479 (Ensembl)
POLE3GeneProductENSG00000148229 (Ensembl)
POLE4GeneProductENSG00000115350 (Ensembl)
POLEGeneProductENSG00000177084 (Ensembl)
POLHGeneProductENSG00000170734 (Ensembl) DNA polymerase eta
POLKGeneProductENSG00000122008 (Ensembl) DNA polymerase kappa
RAD18GeneProductRAD18 (HGNC)
RAD23AGeneProductENSG00000179262 (Ensembl)
RAD23BGeneProductENSG00000119318 (Ensembl)
RBX1GeneProductENSG00000100387 (Ensembl)
RFC1GeneProductENSG00000035928 (Ensembl)
RFC2GeneProductENSG00000049541 (Ensembl)
RFC3GeneProductENSG00000133119 (Ensembl)
RFC4GeneProductENSG00000163918 (Ensembl)
RFC5GeneProductENSG00000111445 (Ensembl)
RNA polymerase IIProtein
RPA1GeneProductENSG00000132383 (Ensembl)
RPA2GeneProductENSG00000117748 (Ensembl)
RPA3GeneProductENSG00000106399 (Ensembl)
SLX4GeneProductENSG00000188827 (Ensembl)
SLX4IPGeneProductENSG00000149346 (Ensembl)
TFIISGeneProduct
TTDA/GTF2H5GeneProductENSG00000272047 (Ensembl)
USP7GeneProductENSG00000187555 (Ensembl)
UVSSAGeneProductENSG00000163945 (Ensembl)
XAB2GeneProductENSG00000076924 (Ensembl)
XPAGeneProductENSG00000136936 (Ensembl)
XPB/ERCC3GeneProductENSG00000163161 (Ensembl)
XPCGeneProductENSG00000154767 (Ensembl)
XPD/ERCC2GeneProductENSG00000104884 (Ensembl)
XPE (DDB2)GeneProductENSG00000134574 (Ensembl) Structural analysis revealed that DDB2 interacts extensively with DNA containing a lesion, while DDB1 stabilizes DDB2 but does not bind to DNA. DDB2 unwinds and kinks the DNA, and the lesion is consequently flipped out and partially held in a shallow binding pocket of DDB2
XPF/ERCC1GeneProductENSG00000012061 (Ensembl)
XPG/ERCC4GeneProductENSG00000175595 (Ensembl)
XRCC1GeneProductENSG00000073050 (Ensembl)
p34 /GTF2H3GeneProductENSG00000111358 (Ensembl)
p44/GTF2H2GeneProductENSG00000145736 (Ensembl)
p52/GTF2H4GeneProductENSG00000213780 (Ensembl)
p62/GTF2H1GeneProductENSG00000110768 (Ensembl)

Annotated Interactions

No annotated interactions

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