ERCC5 (xeroderma pigmentosum, complementation group G)

2001-05-01   Anne Stary , Alain Sarasin 

Laboratory of Genetic Instability, Cancer, UPR2169 CNRS, Institut de Recherches sur le Cancer, 7, rue guy Moquet, BP 8, 94801 VILLEJUIF, France


Atlas Image
XPG (13q32-33) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.



30 kb; 15 exons (from 61 to 1074 bp) and 14 introns (250 to 5763 bp)


  • 15 exons
  • Six spliced XPG mRNA isoforms retaining alternatively spliced exons (I,III), full intron retentions (II, VI), partial intron retention (V) and partial exon skipping (IV)
  • Proteins


    xeroderma pigmentosum group G complementing factor; DNA-repair protein complementing XPG cells


    The XPG protein has DNA endonuclease activity without preference for damaged DNA and is responsible for the 3 incision made during Nucleotide Excision Repair (NER). At the site of a lesion NER proteins create a DNA bubble structure over a length of approximately 25 nucleotides and the XPG protein incises the damaged DNA strand 0-2 nucleotides 3 to the ssDNA-dsDNA junction. In most studies the 3-incision made by the XPG protein appeared to be performed prior to and independently of the 5-incision by XPF-ERCC1. The XPG protein is required non-enzymatically for subsequent 5=D5incision by the XPF/ERCC1 heterodimer during the NER process. Patients belonging to the XP-G complementation group clinically exhibit heterogeneous symptoms, from mild to very severe, sometimes associated with CS. XP-G cells are almost completely repair-deficient and as UV-sensitive as XP-A cells. About half of the described XPG patients exhibit also CS symptoms. In that case, the XPG protein is also involved in the transcription-coupled repair of oxidative DNA lesions.


    Extensive sequence similarities, in bipartite domain A and B, to products of RAD repair genes of two yeasts, Saccharomyces cerevisae RAD2 and Schizosaccharomyces pombe RAD13



    5 XPG sequence alterations: 3 point mutations and two small deletions

    Implicated in

    Entity name
    xeroderma pigmentosum, XP group G / cockayne=D5s syndrome, XP/CS
    Early skin tumours


    Pubmed IDLast YearTitleAuthors
    76977161995Mammalian DNA nucleotide excision repair reconstituted with purified protein components.Aboussekhra A et al
    112595782001Strong functional interactions of TFIIH with XPC and XPG in human DNA nucleotide excision repair, without a preassembled repairosome.Araújo SJ et al
    110372992001Xeroderma pigmentosum and related disorders: defects in DNA repair and transcription.Berneburg M et al
    99277291999Nucleotide excision repair 3' endonuclease XPG stimulates the activity of base excision repairenzyme thymine glycol DNA glycosylase.Bessho T et al
    111049042001Induced mutagenic effects in the nucleotide excision repair deficient Drosophila mutant mus201(D1), expressing a truncated XPG protein.Calléja FM et al
    109109542000Reduced expression levels of nucleotide excision repair genes in lung cancer: a case-control analysis.Cheng L et al
    76514641995XPG protein has a structure-specific endonuclease activity.Cloud KG et al
    100261811999Conserved residues of human XPG protein important for nuclease activity and function in nucleotide excision repair.Constantinou A et al
    90200841997Defective transcription-coupled repair of oxidative base damage in Cockayne syndrome patients from XP group G.Cooper PK et al
    112665442001The human XPG gene: gene architecture, alternative splicing and single nucleotide polymorphisms.Emmert S et al
    90343441997Open complex formation around a lesion during nucleotide excision repair provides a structure for cleavage by human XPG protein.Evans E et al
    93518361997Mechanism of open complex and dual incision formation by human nucleotide excision repair factors.Evans E et al
    93059161997The DNA repair endonuclease XPG binds to proliferating cell nuclear antigen (PCNA) and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21.Gary R et al
    80787651994Human xeroderma pigmentosum group G gene encodes a DNA endonuclease.Habraken Y et al
    88189511996Xeroderma pigmentosum--Cockayne syndrome complex: a further case.Hamel BC et al
    108395262000DNA repair. The bases for Cockayne syndrome.Hanawalt PC et al
    100229221999Postnatal growth failure, short life span, and early onset of cellular senescence and subsequent immortalization in mice lacking the xeroderma pigmentosum group G gene.Harada YN et al
    77003861995RPA involvement in the damage-recognition and incision steps of nucleotide excision repair.He Z et al
    86525571996Interactions involving the human RNA polymerase II transcription/nucleotide excision repair complex TFIIH, the nucleotide excision repair protein XPG, and Cockayne syndrome group B (CSB) protein.Iyer N et al
    100248771999Base excision repair of oxidative DNA damage activated by XPG protein.Klungland A et al
    86327791996Multiple nuclear localization signals in XPG nuclease.Knauf JA et al
    107868322000Transcription-coupled repair of 8-oxoguanine: requirement for XPG, TFIIH, and CSB and implications for Cockayne syndrome.Le Page F et al
    84132381993Human ERCC5 cDNA-cosmid complementation for excision repair and bipartite amino acid domains conserved with RAD proteins of Saccharomyces cerevisiae and Schizosaccharomyces pombe.MacInnes MA et al
    86266441996Replication protein A confers structure-specific endonuclease activities to the XPF-ERCC1 and XPG subunits of human DNA repair excision nuclease.Matsunaga T et al
    86609471996Roles of XPG and XPF/ERCC1 endonucleases in UV-induced immunostaining of PCNA in fibroblasts.Miura M et al
    88233751996DNA repair and ultraviolet mutagenesis in cells from a new patient with xeroderma pigmentosum group G and cockayne syndrome resemble xeroderma pigmentosum cells.Moriwaki S et al
    36203471987Xeroderma pigmentosum complementation group G--report of two cases.Norris PG et al
    106697342000Terminally differentiated human neurons repair transcribed genes but display attenuated global DNA repair and modulation of repair gene expression.Nouspikel T et al
    80902251994XPG endonuclease makes the 3' incision in human DNA nucleotide excision repair.O'Donovan A et al
    75041871994Complementation of xeroderma pigmentosum cells by microinjection of mRNA fractionated under denaturing conditions: an estimation of sizes of XP-E and XP-G mRNA.Okuno Y et al
    87108771996Ultraviolet-induced movement of the human DNA repair protein, Xeroderma pigmentosum type G, in the nucleus.Park MS et al
    93469281997Characterization of a putative helix-loop-helix motif in nucleotide excision repair endonuclease, XPG.Park MS et al
    80888061994The human gene for xeroderma pigmentosum complementation group G (XPG) maps to 13q33 by fluorescence in situ hybridization.Samec S et al
    84835041993Complementation of the DNA repair defect in xeroderma pigmentosum group G cells by a human cDNA related to yeast RAD2.Scherly D et al
    75103661994An ERCC5 gene with homology to yeast RAD2 is involved in group G xeroderma pigmentosum.Shiomi T et al
    96780651998Enhancement of XPG mRNA expression by human interferon-beta in Cockayne syndrome cells.Sugita K et al
    113406412001Purkinje cell degeneration in mice lacking the xeroderma pigmentosum group G gene.Sun XZ et al
    98643911999Enhancement of XPG mRNA transcription by human interferon-beta in Cockayne syndrome cells with complementation group B.Suzuki Y et al
    14839241992Precise localization of the excision repair gene, ERCC5, to human chromosome 13q32.3-q33.1 by direct R-banding fluorescence in situ hybridization.Takahashi E et al
    83174831993Xeroderma pigmentosum complementation group G associated with Cockayne syndrome.Vermeulen W et al
    77999361995An XPG DNA repair defect causing mutagen hypersensitivity in mouse leukemia L1210 cells.Vilpo JA et al
    96184701998Assembly, subunit composition, and footprint of human DNA repair excision nuclease.Wakasugi M et al
    111410662001Novel functional interactions between nucleotide excision DNA repair proteins influencing the enzymatic activities of TFIIH, XPG, and ERCC1-XPF.Winkler GS et al
    81620191994Assignment of a second locus for multiple exostoses to the pericentromeric region of chromosome 11.Wu YQ et al
    112282682001Xeroderma pigmentosum group G with severe neurological involvement and features of Cockayne syndrome in infancy.Zafeiriou DI et al
    95537211998Retrovirus-mediated DNA repair gene transfer into xeroderma pigmentosum cells: perspectives for a gene therapy.Zeng L et al
    108915492000Computer based analyses of the 5'-flanking regions of selected genes involved in the nucleotide excision repair complex.Zhong X et al
    101979771999Molecular mechanism of nucleotide excision Laat WL et al

    Other Information

    Locus ID:

    NCBI: 2073
    MIM: 133530
    HGNC: 3437
    Ensembl: ENSG00000134899


    dbSNP: 2073
    ClinVar: 2073
    TCGA: ENSG00000134899


    Gene IDTranscript IDUniprot

    Expression (GTEx)



    PathwaySourceExternal ID
    Nucleotide excision repairKEGGko03420
    Nucleotide excision repairKEGGhsa03420
    DNA RepairREACTOMER-HSA-73894
    Nucleotide Excision RepairREACTOMER-HSA-5696398
    Global Genome Nucleotide Excision Repair (GG-NER)REACTOMER-HSA-5696399
    Formation of Incision Complex in GG-NERREACTOMER-HSA-5696395
    Dual Incision in GG-NERREACTOMER-HSA-5696400
    Transcription-Coupled Nucleotide Excision Repair (TC-NER)REACTOMER-HSA-6781827
    Dual incision in TC-NERREACTOMER-HSA-6782135

    Protein levels (Protein atlas)

    Not detected


    Entity IDNameTypeEvidenceAssociationPKPDPMIDs
    PA445204Ovarian NeoplasmsDiseaseClinicalAnnotationassociatedPD22158331


    Pubmed IDYearTitleCitations
    161952372006Polymorphisms of DNA repair genes and risk of non-small cell lung cancer.112
    223712962012Polymorphisms in the XPG gene and risk of gastric cancer in Chinese populations.97
    162467222005Recognition of RNA polymerase II and transcription bubbles by XPG, CSB, and TFIIH: insights for transcription-coupled repair and Cockayne Syndrome.86
    174666252007XPG stabilizes TFIIH, allowing transactivation of nuclear receptors: implications for Cockayne syndrome in XP-G/CS patients.76
    166090222006Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer.71
    187014352008Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk.63
    191163882009A field synopsis on low-penetrance variants in DNA repair genes and cancer susceptibility.63
    270193102016Association of potentially functional variants in the XPG gene with neuroblastoma risk in a Chinese population.63
    146880162004Polymorphisms in DNA repair and metabolic genes in bladder cancer.62
    172995782007Genetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk: a meta-analysis.58


    Anne Stary ; Alain Sarasin

    ERCC5 (xeroderma pigmentosum, complementation group G)

    Atlas Genet Cytogenet Oncol Haematol. 2001-05-01

    Online version: