Nucleotide excision repair in xeroderma pigmentosum (WP5114)

Homo sapiens

This pathway describes the process of Nucleotide Excision Repair (NER) in Xeroderma Pigmentosum (XP).


Natalie Hinkova , Friederike Ehrhart , Egon Willighagen , and Eric Weitz


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Homo sapiens


Rare Diseases


Pathway Ontology

nucleotide excision repair pathway DNA repair pathway

Disease Ontology

Cockayne syndrome xeroderma pigmentosum


Label Type Compact URI Comment
ERCC6 (CSB) GeneProduct ensembl:ENSG00000225830
TTDA/GTF2H5 GeneProduct ensembl:ENSG00000272047
p52/GTF2H4 GeneProduct ensembl:ENSG00000213780
BRCA1 GeneProduct hgnc.symbol:BRCA1
SLX4 GeneProduct ensembl:ENSG00000188827
XAB2 GeneProduct ensembl:ENSG00000076924
POLK GeneProduct ensembl:ENSG00000122008 DNA polymerase kappa
CHD1L (ALC1) GeneProduct ensembl:ENSG00000131778
RPA3 GeneProduct ensembl:ENSG00000106399
USP7 GeneProduct ensembl:ENSG00000187555
UVSSA GeneProduct ensembl:ENSG00000163945
XRCC1 GeneProduct ensembl:ENSG00000073050
PARP1 GeneProduct hgnc.symbol:PARP1
ERCC6 GeneProduct ensembl:ENSG00000225830
RPA2 GeneProduct ensembl:ENSG00000117748
HMGN1 GeneProduct ensembl:ENSG00000205581
RPA1 GeneProduct ensembl:ENSG00000132383
SLX4IP GeneProduct ensembl:ENSG00000149346
RAD23B GeneProduct ensembl:ENSG00000119318
XPA GeneProduct ensembl:ENSG00000136936 'Furthermore, the DDB2 complex-mediated ubiquitylation plays a role in recruiting XPA to damaged sites'.
One of the key roles of XPA is to coordinate the assembly of other NER core factors around the DNA damage site before lesion excision
XPA functions in damage verification step in NER, as well as a molecular scaffold to assemble other NER core factors around the DNA damage site
XPA GeneProduct ensembl:ENSG00000136936
RAD18 GeneProduct hgnc.symbol:RAD18
POLD1 GeneProduct ensembl:ENSG00000062822
LIG3 GeneProduct ensembl:ENSG00000005156
POLH GeneProduct ensembl:ENSG00000170734 DNA polymerase eta
LIG1 GeneProduct ensembl:ENSG00000105486
RBX1 GeneProduct ensembl:ENSG00000100387
CUL4A GeneProduct ensembl:ENSG00000139842
CUL4B GeneProduct ensembl:ENSG00000158290
ERCC8 (CSA) GeneProduct ensembl:ENSG00000049167
DDB1 GeneProduct ensembl:ENSG00000167986
CDK7 GeneProduct ensembl:ENSG00000134058 This subcomplex dissociates after XPA binds
MNAT1 GeneProduct ensembl:ENSG00000020426
CCNH GeneProduct ensembl:ENSG00000134480
XPD/ERCC2 GeneProduct ensembl:ENSG00000104884
XPB/ERCC3 GeneProduct ensembl:ENSG00000163161
p62/GTF2H1 GeneProduct ensembl:ENSG00000110768
p44/GTF2H2 GeneProduct ensembl:ENSG00000145736
p34 /GTF2H3 GeneProduct ensembl:ENSG00000111358
XPF/ERCC1 GeneProduct ensembl:ENSG00000012061
XPG/ERCC4 GeneProduct ensembl:ENSG00000175595
POLD2 GeneProduct ensembl:ENSG00000106628
POLD3 GeneProduct ensembl:ENSG00000077514 DNA polymerase delta
POLD4 GeneProduct ensembl:ENSG00000175482
POLE GeneProduct ensembl:ENSG00000177084
POLE2 GeneProduct ensembl:ENSG00000100479
POLE3 GeneProduct ensembl:ENSG00000148229
POLE4 GeneProduct ensembl:ENSG00000115350
PCNA GeneProduct ensembl:ENSG00000132646
RFC1 GeneProduct ensembl:ENSG00000035928
RFC2 GeneProduct ensembl:ENSG00000049541
RFC3 GeneProduct ensembl:ENSG00000133119
RFC4 GeneProduct ensembl:ENSG00000163918
RFC5 GeneProduct ensembl:ENSG00000111445
XPE (DDB2) GeneProduct ensembl:ENSG00000134574 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
XPC GeneProduct ensembl:ENSG00000154767
RAD23A GeneProduct ensembl:ENSG00000179262
CETN2 GeneProduct ensembl:ENSG00000147400 'CENTRIN 2 enhances the affinity of XPC/RAD23B for DNA distortions'
BRCA1 GeneProduct ensembl:ENSG00000012048
CSN (COP9) Protein uniprot:A0A096LP07
Histone H2A Protein uniprot:A0A024R017
Histone H3 Protein uniprot:B2R4P9
Histone H4 Protein uniprot:B2R4R0


  1. 3-Methyladenine-DNA glycosylase (MPG protein) interacts with human RAD23 proteins. Miao F, Bouziane M, Dammann R, Masutani C, Hanaoka F, Pfeifer G, et al. J Biol Chem. 2000 Sep 15;275(37):28433–8. PubMed Europe PMC Scholia
  2. Human XPA and RPA DNA repair proteins participate in specific recognition of triplex-induced helical distortions. Vasquez KM, Christensen J, Li L, Finch RA, Glazer PM. Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):5848–53. PubMed Europe PMC Scholia
  3. Sequential binding of UV DNA damage binding factor and degradation of the p48 subunit as early events after UV irradiation. Rapić-Otrin V, McLenigan MP, Bisi DC, Gonzalez M, Levine AS. Nucleic Acids Res. 2002 Jun 1;30(11):2588–98. PubMed Europe PMC Scholia
  4. The PCNA-RFC families of DNA clamps and clamp loaders. Majka J, Burgers PMJ. Prog Nucleic Acid Res Mol Biol. 2004;78:227–60. PubMed Europe PMC Scholia
  5. UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex. Sugasawa K, Okuda Y, Saijo M, Nishi R, Matsuda N, Chu G, et al. Cell. 2005 May 6;121(3):387–400. PubMed Europe PMC Scholia
  6. The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites. Kapetanaki MG, Guerrero-Santoro J, Bisi DC, Hsieh CL, Rapić-Otrin V, Levine AS. Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2588–93. PubMed Europe PMC Scholia
  7. CSA-dependent degradation of CSB by the ubiquitin-proteasome pathway establishes a link between complementation factors of the Cockayne syndrome. Groisman R, Kuraoka I, Chevallier O, Gaye N, Magnaldo T, Tanaka K, et al. Genes Dev. 2006 Jun 1;20(11):1429–34. PubMed Europe PMC Scholia
  8. RETRACTED: Sealing of chromosomal DNA nicks during nucleotide excision repair requires XRCC1 and DNA ligase III alpha in a cell-cycle-specific manner. Moser J, Kool H, Giakzidis I, Caldecott K, Mullenders LHF, Fousteri MI. Mol Cell. 2007 Jul 20;27(2):311–23. PubMed Europe PMC Scholia
  9. Sequential recruitment of the repair factors during NER: the role of XPG in initiating the resynthesis step. Mocquet V, Lainé JP, Riedl T, Yajin Z, Lee MY, Egly JM. EMBO J. 2008 Jan 9;27(1):155–67. PubMed Europe PMC Scholia
  10. Cooperation of replication protein A with the ubiquitin ligase Rad18 in DNA damage bypass. Huttner D, Ulrich HD. Cell Cycle. 2008 Dec;7(23):3629–33. PubMed Europe PMC Scholia
  11. Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells. Ogi T, Limsirichaikul S, Overmeer RM, Volker M, Takenaka K, Cloney R, et al. Mol Cell. 2010 Mar 12;37(5):714–27. PubMed Europe PMC Scholia
  12. DDB2 complex-mediated ubiquitylation around DNA damage is oppositely regulated by XPC and Ku and contributes to the recruitment of XPA. Takedachi A, Saijo M, Tanaka K. Mol Cell Biol. 2010 Jun;30(11):2708–23. PubMed Europe PMC Scholia
  13. Role of endonucleases XPF and XPG in nucleotide excision repair of platinated DNA and cisplatin/oxaliplatin cytotoxicity. Graf N, Ang WH, Zhu G, Myint M, Lippard SJ. Chembiochem. 2011 May 2;12(7):1115–23. PubMed Europe PMC Scholia
  14. Differential contribution of XPC, RAD23A, RAD23B and CENTRIN 2 to the UV-response in human cells. Renaud E, Miccoli L, Zacal N, Biard DS, Craescu CT, Rainbow AJ, et al. DNA Repair (Amst). 2011 Aug 15;10(8):835–47. PubMed Europe PMC Scholia
  15. The hMsh2-hMsh6 complex acts in concert with monoubiquitinated PCNA and Pol η in response to oxidative DNA damage in human cells. Zlatanou A, Despras E, Braz-Petta T, Boubakour-Azzouz I, Pouvelle C, Stewart GS, et al. Mol Cell. 2011 Aug 19;43(4):649–62. PubMed Europe PMC Scholia
  16. The molecular basis of CRL4DDB2/CSA ubiquitin ligase architecture, targeting, and activation. Fischer ES, Scrima A, Böhm K, Matsumoto S, Lingaraju GM, Faty M, et al. Cell. 2011 Nov 23;147(5):1024–39. PubMed Europe PMC Scholia
  17. Essential role of the CUL4B ubiquitin ligase in extra-embryonic tissue development during mouse embryogenesis. Liu L, Yin Y, Li Y, Prevedel L, Lacy EH, Ma L, et al. Cell Res. 2012 Aug;22(8):1258–69. PubMed Europe PMC Scholia
  18. DDB2 promotes chromatin decondensation at UV-induced DNA damage. Luijsterburg MS, Lindh M, Acs K, Vrouwe MG, Pines A, van Attikum H, et al. J Cell Biol. 2012 Apr 16;197(2):267–81. PubMed Europe PMC Scholia
  19. PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1. Pines A, Vrouwe MG, Marteijn JA, Typas D, Luijsterburg MS, Cansoy M, et al. J Cell Biol. 2012 Oct 15;199(2):235–49. PubMed Europe PMC Scholia
  20. BRCA1 promotes the ubiquitination of PCNA and recruitment of translesion polymerases in response to replication blockade. Tian F, Sharma S, Zou J, Lin SY, Wang B, Rezvani K, et al. Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):13558–63. PubMed Europe PMC Scholia
  21. Mammalian transcription-coupled excision repair. Vermeulen W, Fousteri M. Cold Spring Harb Perspect Biol. 2013 Aug 1;5(8):a012625. PubMed Europe PMC Scholia
  22. Role of the XPA protein in the NER pathway: A perspective on the function of structural disorder in macromolecular assembly. Fadda E. Comput Struct Biotechnol J. 2015 Dec 8;14:78–85. PubMed Europe PMC Scholia
  23. Common TFIIH recruitment mechanism in global genome and transcription-coupled repair subpathways. Okuda M, Nakazawa Y, Guo C, Ogi T, Nishimura Y. Nucleic Acids Res. 2017 Dec 15;45(22):13043–55. PubMed Europe PMC Scholia
  24. The transcription-coupled DNA repair-initiating protein CSB promotes XRCC1 recruitment to oxidative DNA damage. Menoni H, Wienholz F, Theil AF, Janssens RC, Lans H, Campalans A, et al. Nucleic Acids Res. 2018 Sep 6;46(15):7747–56. PubMed Europe PMC Scholia
  25. SLX4IP acts with SLX4 and XPF-ERCC1 to promote interstrand crosslink repair. Zhang H, Chen Z, Ye Y, Ye Z, Cao D, Xiong Y, et al. Nucleic Acids Res. 2019 Nov 4;47(19):10181–201. PubMed Europe PMC Scholia
  26. XPA: DNA Repair Protein of Significant Clinical Importance. Borszéková Pulzová L, Ward TA, Chovanec M. Int J Mol Sci. 2020 Mar 22;21(6):2182. PubMed Europe PMC Scholia
  27. Ubiquitinated-PCNA protects replication forks from DNA2-mediated degradation by regulating Okazaki fragment maturation and chromatin assembly. Thakar T, Leung W, Nicolae CM, Clements KE, Shen B, Bielinsky AK, et al. Nat Commun. 2020 May 1;11(1):2147. PubMed Europe PMC Scholia
  28. The involvement of nucleotide excision repair proteins in the removal of oxidative DNA damage. Kumar N, Raja S, Van Houten B. Nucleic Acids Res. 2020 Nov 18;48(20):11227–43. PubMed Europe PMC Scholia