ERCC4 (xeroderma pigmentosum, complementation group F)

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

Identity

HGNC
LOCATION
16p13.12
IMAGE
Atlas Image
LEGEND
XPF (16p13) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
LOCUSID
ALIAS
ERCC11,FANCQ,RAD1,XFEPS,XPF
FUSION GENES

DNA/RNA

Description

28.2 kb

Transcription

2881 bp =D0 11 exons

Proteins

Description

  • xeroderma pigmentosum group F complementing factor; DNA-repair protein complementing XPF cells 905 amino acids; form a stable complex with the ERCC1 protein; The XPF protein and the ERCC1 protein form a complex that exhibits structure specific endonuclease activity that is responsible for the 5 incision during the NER reaction. XPF-ERCC1 also binds to XPA (through ERCC1) and to RPA (through XPF) but not preferentially to damaged DNA. At the site of a lesion Nucleotide Excision Repair (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 made prior to and independently of the 5-incision by XPF-ERCC1. XP-F patients have a relatively mild XP phenotype without neurological abnormalities. Cells from XP-F patients are slightly UV-sensitive and exhibit low levels of repair initially after UV-irradiation.
  • The XPF protein is a single-stranded DNA endonuclease that is also involved in a pathway of recombination repair of DNA interstrand crosslinks.
  • Homology

    Substantial homology with the eucaryotic DNA repair and recombination proteins MEI-9 (Drosophila melanogaster), Rad16 (Saccharomyces cerevisae) and Rad1 (Schizosaccharomyces pombe).

    Mutations

    Germinal

    9 point mutations ; 3 small deletions ; 1 small insertion ; 1 gross deletion

    Implicated in

    Entity name
    xeroderma pigmentosum, XP group F
    Disease
    Early skin tumours in XPF patients

    Bibliography

    Pubmed IDLast YearTitleAuthors
    76977161995Mammalian DNA nucleotide excision repair reconstituted with purified protein components.Aboussekhra A et al
    106735062000Nucleotide excision repair of DNA with recombinant human proteins: definition of the minimal set of factors, active forms of TFIIH, and modulation by CAK.Araújo SJ et al
    90136421997Reconstitution of human excision nuclease with recombinant XPF-ERCC1 complex.Bessho T et al
    82530901993Co-correction of the ERCC1, ERCC4 and xeroderma pigmentosum group F DNA repair defects in vitro.Biggerstaff M et al
    94472311997Excision-repair patch lengths are similar for transcription-coupled repair and global genome repair in UV-irradiated human cells.Bowman KK et al
    88876841996ERCC4 (XPF) encodes a human nucleotide excision repair protein with eukaryotic recombination homologs.Brookman KW et al
    112851942001Genetic polymorphisms in DNA repair genes and risk of lung cancer.Butkiewicz D et al
    93518361997Mechanism of open complex and dual incision formation by human nucleotide excision repair factors.Evans E et al
    111609182001Activity of individual ERCC1 and XPF subunits in DNA nucleotide excision repair.Gaillard PHL et al
    96534531998ERCC1 mutations in UV-sensitive Chinese hamster ovary (CHO) cell lines.Hayashi T et al
    103203751999Action of DNA repair endonuclease ERCC1/XPF in living cells.Houtsmuller AB et al
    26647291989Late onset of skin cancers in 2 xeroderma pigmentosum group F siblings and a review of 30 Japanese xeroderma pigmentosum patients in groups D, E and F.Kondo S et al
    83320821993Regional mapping of human DNA excision repair gene ERCC4 to chromosome 16p13.13-p13.2.Liu P et al
    95806601998Characterization of molecular defects in xeroderma pigmentosum group F in relation to its clinically mild symptoms.Matsumura Y 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
    104135171999Domain mapping of the DNA binding, endonuclease, and ERCC1 binding properties of the human DNA repair protein XPF.McCutchen-Maloney SL et al
    84278281993A case of xeroderma pigmentosum complementation group F with neurological abnormalities.Moriwaki S et al
    86265231996Reaction mechanism of human DNA repair excision nuclease.Mu D et al
    86136811996ERCC1/ERCC4 5'-endonuclease activity as a determinant of hypoxic cell radiosensitivity.Murray D et al
    18144241991Xeroderma pigmentosum patients belonging to complementation group F and efficient liquid-holding recovery of ultraviolet damage.Nishigori C 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
    75593821995Purification and characterization of the XPF-ERCC1 complex of human DNA repair excision nuclease.Park CH et al
    81971751994Formation of a ternary complex by human XPA, ERCC1, and ERCC4(XPF) excision repair proteins.Park CH et al
    29295931989Human chromosome 15 confers partial complementation of phenotypes to xeroderma pigmentosum group F cells.Saxon PJ et al
    95795551998Homozygous R788W point mutation in the XPF gene of a patient with xeroderma pigmentosum and late-onset neurologic disease.Sijbers AM et al
    80417091994Molecular cloning of the human nucleotide-excision-repair gene ERCC4.Thompson LH et al
    91885071997The non-catalytic function of XPG protein during dual incision in human nucleotide excision repair.Wakasugi M et al
    91972401997Disruption of mouse ERCC1 results in a novel repair syndrome with growth failure, nuclear abnormalities and senescence.Weeda G 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
    102149081999DNA damage recognition during nucleotide excision repair in mammalian cells.Wood RD et al
    98621901998Sensitivity of group F xeroderma pigmentosum cells to UV and mitomycin C relative to levels of XPF and ERCC1 overexpression.Yagi T et al
    94726931998Complete restoration of normal DNA repair characteristics in group F xeroderma pigmentosum cells by over-expression of transfected XPF cDNA.Yagi T et al
    20399951991Analysis of point mutations in an ultraviolet-irradiated shuttle vector plasmid propagated in cells from Japanese xeroderma pigmentosum patients in complementation groups A and F.Yagi T et al
    90250961997A low content of ERCC1 and a 120 kDa protein is a frequent feature of group F xeroderma pigmentosum fibroblast cells.Yagi T et al
    63210521984Xeroderma pigmentosum fibroblasts are more sensitive to asbestos fibers than are normal human fibroblasts.Yang LL et al
    95258761998DNA structural elements required for ERCC1-XPF endonuclease activity.de Laat WL et al
    75963551995Partial characterization of the DNA repair protein complex, containing the ERCC1, ERCC4, ERCC11 and XPF correcting activities.van Vuuren AJ et al

    Other Information

    Locus ID:

    NCBI: 2072
    MIM: 133520
    HGNC: 3436
    Ensembl: ENSG00000175595

    Variants:

    dbSNP: 2072
    ClinVar: 2072
    TCGA: ENSG00000175595
    COSMIC: ERCC4

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000175595ENST00000311895Q92889
    ENSG00000175595ENST00000311895A0A1W1GSK9
    ENSG00000175595ENST00000462862I3L4K0
    ENSG00000175595ENST00000574194I3NI48
    ENSG00000175595ENST00000575156Q92889
    ENSG00000175595ENST00000575156A0A1W1GSP5

    Expression (GTEx)

    0
    5
    10
    15

    Pathways

    PathwaySourceExternal ID
    Nucleotide excision repairKEGGko03420
    Nucleotide excision repairKEGGhsa03420
    Fanconi anemia pathwayKEGGko03460
    Fanconi anemia pathwayKEGGhsa03460
    DNA RepairREACTOMER-HSA-73894
    DNA Double-Strand Break RepairREACTOMER-HSA-5693532
    Homology Directed RepairREACTOMER-HSA-5693538
    HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)REACTOMER-HSA-5693567
    HDR through Single Strand Annealing (SSA)REACTOMER-HSA-5685938
    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
    Fanconi Anemia PathwayREACTOMER-HSA-6783310

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High

    PharmGKB

    Entity IDNameTypeEvidenceAssociationPKPDPMIDs
    PA164713176Platinum compoundsChemicalClinicalAnnotationassociatedPD25069034
    PA443622Carcinoma, Non-Small-Cell LungDiseaseClinicalAnnotationassociatedPD25069034

    References

    Pubmed IDYearTitleCitations
    146906022003ERCC1/XPF removes the 3' overhang from uncapped telomeres and represses formation of telomeric DNA-containing double minute chromosomes.139
    161952372006Polymorphisms of DNA repair genes and risk of non-small cell lung cancer.112
    166090222006Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer.71
    218966582011Human SNM1A and XPF-ERCC1 collaborate to initiate DNA interstrand cross-link repair.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
    150952992004Reduced levels of XPA, ERCC1 and XPF DNA repair proteins in testis tumor cell lines.60
    172995782007Genetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk: a meta-analysis.58
    160769552005Crystal structure and DNA binding functions of ERCC1, a subunit of the DNA structure-specific endonuclease XPF-ERCC1.57
    183961112008ERCC1/XPF limits L1 retrotransposition.51

    Citation

    Anne Stary ; Alain Sarasin

    ERCC4 (xeroderma pigmentosum, complementation group F)

    Atlas Genet Cytogenet Oncol Haematol. 2001-05-01

    Online version: http://atlasgeneticsoncology.org/gene/299/ercc4-(xeroderma-pigmentosum-complementation-group-f)