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XPF (xeroderma pigmentosum, complementation group F)

Identity

Other namesERCC4
Hugo ERCC4
Location 16p13.1-13.2
 
  XPF (16p13) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome : contact rocchi@biologia.uniba.it

DNA/RNA

Description 28.2 kb
Transcription 2881 bp =D0 11 exons

Protein

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

    External links

    Nomenclature
    HugoERCC4
    GDBERCC4
    Entrez_GeneERCC4  2072  excision repair cross-complementing rodent repair deficiency, complementation group 4
    Cards
    AtlasXPFID299
    GeneCardsERCC4
    EnsemblERCC4 [Search_View]   ENSG00000175595 [Gene_View]
    GenatlasERCC4
    GeneLynxERCC4
    eGenomeERCC4
    euGene2072
    Genomic and cartography
    GoldenPathERCC4  -     chr16:13921524-13949704 +  16p13.3-p13.11   [Description]    (hg18-Mar_2006)
    EnsemblERCC4 - 16p13.3-p13.11 [CytoView]
    NCBIMapview
    OMIMDisease map [OMIM]
    HomoloGeneERCC4
    Gene and transcription
    GenbankAI470593 [ ENTREZ ]
    GenbankAK289726 [ ENTREZ ]
    GenbankBC020741 [ ENTREZ ]
    GenbankBC142631 [ ENTREZ ]
    GenbankU64315 [ ENTREZ ]
    RefSeqNM_005236 [ SRS ]    NM_005236 [ ENTREZ ]
    RefSeqAC_000059 [ SRS ]    AC_000059 [ ENTREZ ]
    RefSeqNC_000016 [ SRS ]    NC_000016 [ ENTREZ ]
    RefSeqNT_010393 [ SRS ]    NT_010393 [ ENTREZ ]
    RefSeqNW_926018 [ SRS ]    NW_926018 [ ENTREZ ]
    AceViewERCC4 AceView - NCBI
    UnigeneHs.697271 [ SRS ]    Hs.697271 [ NCBI ]     HS697271 [ spliceNest ]
    Fast-db3732 (alternative variants)
    Protein : pattern, domain, 3D structure
    SwissProtQ92889 [ SRS]    Q92889 [ EXPASY ]     Q92889 [ INTERPRO ]
    InterproIPR006166 DNA_repair_nuc_XPF/helicase [ SRS ]    IPR006166 DNA_repair_nuc_XPF/helicase [ EBI ]
    InterproIPR006167 Rad1 [ SRS ]    IPR006167 Rad1 [ EBI ]
    CluSTrQ92889
    PfamPF02732 ERCC4 [ SRS ]    PF02732 ERCC4 [ Sanger ]    pfam02732 [ NCBI-CDD ]
    BlocksQ92889
    PDB1Z00 [ SRS ]    1Z00 [ PdbSum ],   1Z00 [ IMB ]   1Z00 [ RSDB ]
    PDB2A1J [ SRS ]    2A1J [ PdbSum ],   2A1J [ IMB ]   2A1J [ RSDB ]
    PDB2AQ0 [ SRS ]    2AQ0 [ PdbSum ],   2AQ0 [ IMB ]   2AQ0 [ RSDB ]
    HPRD00594
    Protein Interaction databases
    DIPQ92889
    IntActQ92889
    Polymorphism : SNP, mutations, diseases
    OMIM133520;278760;610965    [ map ]   
    GENECLINICS133520;278760;610965
    SNPERCC4 [dbSNP-NCBI]  
    SNPNM_005236 [SNP-NCI]  
    SNPERCC4 [GeneSNPs - Utah]  ERCC4] [HGBASE - SRS]
    HAPMAPERCC4 [HAPMAP]  
    COSMICERCC4 [Somatic mutation (COSMIC-CGP-Sanger)]  
    HGMDERCC4
    General knowledge
    Family BrowserERCC4 [UCSC Family Browser]
    SOURCENM_005236
    SMDHs.697271
    SAGEHs.697271
    Enzyme3.1.-.- [ Enzyme-SRS ]   3.1.-.- [ Brenda-SRS ]   3.1.-.- [ KEGG ]   3.1.-.- [ WIT ]
    GOnucleotide-excision repair complex [Amigo]  nucleotide-excision repair complex
    GOmagnesium ion binding [Amigo]  magnesium ion binding
    GOdouble-strand break repair via homologous recombination [Amigo]  double-strand break repair via homologous recombination
    GOnuclear chromosome, telomeric region [Amigo]  nuclear chromosome, telomeric region
    GOdamaged DNA binding [Amigo]  damaged DNA binding
    GOsingle-stranded DNA binding [Amigo]  single-stranded DNA binding
    GOendodeoxyribonuclease activity [Amigo]  endodeoxyribonuclease activity
    GOendodeoxyribonuclease activity [Amigo]  endodeoxyribonuclease activity
    GOnucleus [Amigo]  nucleus
    GOnucleotide-excision repair, DNA incision, 3'-to lesion [Amigo]  nucleotide-excision repair, DNA incision, 3'-to lesion
    GOnucleotide-excision repair, DNA incision, 5'-to lesion [Amigo]  nucleotide-excision repair, DNA incision, 5'-to lesion
    GOprotein C-terminus binding [Amigo]  protein C-terminus binding
    GOresponse to UV [Amigo]  response to UV
    GOhydrolase activity [Amigo]  hydrolase activity
    GOnegative regulation of telomere maintenance [Amigo]  negative regulation of telomere maintenance
    GOprotein N-terminus binding [Amigo]  protein N-terminus binding
    PubGeneERCC4
    TreeFamERCC4
    CTD2072 [Comparative ToxicoGenomics Database]
    Other databases
    Probes
    ProbeCancer Cytogenetics (Bari)
    ProbeERCC4 Related clones (RZPD - Berlin)
    PubMed
    PubMed33 Pubmed reference(s) in LocusLink

    Bibliography

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    Carcinogenesis. 1984 ; 5 (2) : 291-294.
    PMID 6321052
     
    Late 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.
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    PMID 2664729
     
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    PMID 2929593
     
    Analysis of point mutations in an ultraviolet-irradiated shuttle vector plasmid propagated in cells from Japanese xeroderma pigmentosum patients in complementation groups A and F.
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    PMID 2039995
     
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    PMID 8332082
     
    Co-correction of the ERCC1, ERCC4 and xeroderma pigmentosum group F DNA repair defects in vitro.
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    Formation of a ternary complex by human XPA, ERCC1, and ERCC4(XPF) excision repair proteins.
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    PMID 8041709
     
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    PMID 7596355
     
    Purification and characterization of the XPF-ERCC1 complex of human DNA repair excision nuclease.
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    PMID 7559382
     
    Human DNA repair excision nuclease. Analysis of the roles of the subunits involved in dual incisions by using anti-XPG and anti-ERCC1 antibodies.
    Matsunaga T, Mu D, Park CH, Reardon JT, Sancar A
    The Journal of biological chemistry. 1995 ; 270 (35) : 20862-20869.
    PMID 7657672
     
    Detection of nucleotide excision repair incisions in human fibroblasts by immunostaining for PCNA.
    Aboussekhra A, Wood RD
    Experimental cell research. 1995 ; 221 (2) : 326-332.
    PMID 7493631
     
    Mammalian DNA nucleotide excision repair reconstituted with purified protein components.
    Aboussekhra A, Biggerstaff M, Shivji MK, Vilpo JA, Moncollin V, Podust VN, ProtiŸá M, Hˆºbscher U, Egly JM, Wood RD
    Cell. 1995 ; 80 (6) : 859-868.
    PMID 7697716
     
    ERCC4 (XPF) encodes a human nucleotide excision repair protein with eukaryotic recombination homologs.
    Brookman KW, Lamerdin JE, Thelen MP, Hwang M, Reardon JT, Sancar A, Zhou ZQ, Walter CA, Parris CN, Thompson LH
    Molecular and cellular biology. 1996 ; 16 (11) : 6553-6562.
    PMID 8887684
     
    Reaction mechanism of human DNA repair excision nuclease.
    Mu D, Hsu DS, Sancar A
    The Journal of biological chemistry. 1996 ; 271 (14) : 8285-8294.
    PMID 8626523
     
    Replication protein A confers structure-specific endonuclease activities to the XPF-ERCC1 and XPG subunits of human DNA repair excision nuclease.
    Matsunaga T, Park CH, Bessho T, Mu D, Sancar A
    The Journal of biological chemistry. 1996 ; 271 (19) : 11047-11050.
    PMID 8626644
     
    ERCC1/ERCC4 5'-endonuclease activity as a determinant of hypoxic cell radiosensitivity.
    Murray D, Macann A, Hanson J, Rosenberg E
    International journal of radiation biology. 1996 ; 69 (3) : 319-327.
    PMID 8613681
     
    Xeroderma pigmentosum group F caused by a defect in a structure-specific DNA repair endonuclease.
    Sijbers AM, de Laat WL, Ariza RR, Biggerstaff M, Wei YF, Moggs JG, Carter KC, Shell BK, Evans E, de Jong MC, Rademakers S, de Rooij J, Jaspers NG, Hoeijmakers JH, Wood RD
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    PMID 8797827
     
    Mutational analysis of the human nucleotide excision repair gene ERCC1.
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    Nucleic acids research. 1996 ; 24 (17) : 3370-3380.
    PMID 8811092
     
    The non-catalytic function of XPG protein during dual incision in human nucleotide excision repair.
    Wakasugi M, Reardon JT, Sancar A
    The Journal of biological chemistry. 1997 ; 272 (25) : 16030-16034.
    PMID 9188507
     
    Disruption of mouse ERCC1 results in a novel repair syndrome with growth failure, nuclear abnormalities and senescence.
    Weeda G, Donker I, de Wit J, Morreau H, Janssens R, Vissers CJ, Nigg A, van Steeg H, Bootsma D, Hoeijmakers JH
    Current biology : CB. 1997 ; 7 (6) : 427-439.
    PMID 9197240
     
    Reconstitution of human excision nuclease with recombinant XPF-ERCC1 complex.
    Bessho T, Sancar A, Thompson LH, Thelen MP
    The Journal of biological chemistry. 1997 ; 272 (6) : 3833-3837.
    PMID 9013642
     
    Excision-repair patch lengths are similar for transcription-coupled repair and global genome repair in UV-irradiated human cells.
    Bowman KK, Smith CA, Hanawalt PC
    Mutation research. 1997 ; 385 (2) : 95-105.
    PMID 9447231
     
    Mechanism of open complex and dual incision formation by human nucleotide excision repair factors.
    Evans E, Moggs JG, Hwang JR, Egly JM, Wood RD
    The EMBO journal. 1997 ; 16 (21) : 6559-6573.
    PMID 9351836
     
    A low content of ERCC1 and a 120 kDa protein is a frequent feature of group F xeroderma pigmentosum fibroblast cells.
    Yagi T, Wood RD, Takebe H
    Mutagenesis. 1997 ; 12 (1) : 41-44.
    PMID 9025096
     
    Sensitivity of group F xeroderma pigmentosum cells to UV and mitomycin C relative to levels of XPF and ERCC1 overexpression.
    Yagi T, Katsuya A, Koyano A, Takebe H
    Mutagenesis. 1998 ; 13 (6) : 595-599.
    PMID 9862190
     
    Homozygous R788W point mutation in the XPF gene of a patient with xeroderma pigmentosum and late-onset neurologic disease.
    Sijbers AM, van Voorst Vader PC, Snoek JW, Raams A, Jaspers NG, Kleijer WJ
    The Journal of investigative dermatology. 1998 ; 110 (5) : 832-836.
    PMID 9579555
     
    Complete restoration of normal DNA repair characteristics in group F xeroderma pigmentosum cells by over-expression of transfected XPF cDNA.
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    Carcinogenesis. 1998 ; 19 (1) : 55-60.
    PMID 9472693
     
    Mapping of interaction domains between human repair proteins ERCC1 and XPF.
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    Nucleic acids research. 1998 ; 26 (18) : 4146-4152.
    PMID 9722633
     
    DNA-binding polarity of human replication protein A positions nucleases in nucleotide excision repair.
    de Laat WL, Appeldoorn E, Sugasawa K, Weterings E, Jaspers NG, Hoeijmakers JH
    Genes & development. 1998 ; 12 (16) : 2598-2609.
    PMID 9716411
     
    DNA structural elements required for ERCC1-XPF endonuclease activity.
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    The Journal of biological chemistry. 1998 ; 273 (14) : 7835-7842.
    PMID 9525876
     
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    PMID 9653453
     
    Characterization of molecular defects in xeroderma pigmentosum group F in relation to its clinically mild symptoms.
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    Human molecular genetics. 1998 ; 7 (6) : 969-974.
    PMID 9580660
     
    Action of DNA repair endonuclease ERCC1/XPF in living cells.
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    Science (New York, N.Y.). 1999 ; 284 (5416) : 958-961.
    PMID 10320375
     
    Domain mapping of the DNA binding, endonuclease, and ERCC1 binding properties of the human DNA repair protein XPF.
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    Biochemistry. 1999 ; 38 (29) : 9417-9425.
    PMID 10413517
     
    DNA damage recognition during nucleotide excision repair in mammalian cells.
    Wood RD
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    PMID 10214908
     
    Nucleotide excision repair of DNA with recombinant human proteins: definition of the minimal set of factors, active forms of TFIIH, and modulation by CAK.
    Araˆ†jo SJ, Tirode F, Coin F, Pospiech H, Syvˆ§oja JE, Stucki M, Hˆºbscher U, Egly JM, Wood RD
    Genes & development. 2000 ; 14 (3) : 349-359.
    PMID 10673506
     
    Terminally differentiated human neurons repair transcribed genes but display attenuated global DNA repair and modulation of repair gene expression.
    Nouspikel T, Hanawalt PC
    Molecular and cellular biology. 2000 ; 20 (5) : 1562-1570.
    PMID 10669734
     
    Genetic polymorphisms in DNA repair genes and risk of lung cancer.
    Butkiewicz D, Rusin M, Enewold L, Shields PG, Chorazy M, Harris CC
    Carcinogenesis. 2001 ; 22 (4) : 593-597.
    PMID 11285194
     
    Activity of individual ERCC1 and XPF subunits in DNA nucleotide excision repair.
    Gaillard PH, Wood RD
    Nucleic acids research. 2001 ; 29 (4) : 872-879.
    PMID 11160918
     
    Novel functional interactions between nucleotide excision DNA repair proteins influencing the enzymatic activities of TFIIH, XPG, and ERCC1-XPF.
    Winkler GS, Sugasawa K, Eker AP, de Laat WL, Hoeijmakers JH
    Biochemistry. 2001 ; 40 (1) : 160-165.
    PMID 11141066
     
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    Contributor(s)

    Written05-2001Anne Stary and Alain Sarasin

    Citation

    This paper should be referenced as such :
    Stary A, Sarasin A . XPF (xeroderma pigmentosum, complementation group F). Atlas Genet Cytogenet Oncol Haematol. May 2001 .
    URL : http://AtlasGeneticsOncology.org/Genes/XPFID299.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Wed Jul 2 08:28:08 2008


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