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FLASH GENE
Symbol ERCC4 contributors: mct/npt - updated : 06-06-2016
HGNC name excision repair cross-complementing rodent repair deficiency, complementation group 4
HGNC id 3436
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal binding DNA
  • a C terminal region binding ERCC1 with two leucine zipper domains
  • HOMOLOGY
    interspecies homolog to yeast RAD1
    homolog to Drosophila eukaryotic DNA repair and recombination proteins MEI-9
    homolog to yeast S.cerevisiae RAD16
    intraspecies homolog to ERCC11
    Homologene
    FAMILY
  • XPF family
  • CATEGORY DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome,telomere
    basic FUNCTION
  • single strand DNA endonuclease, binding and hydrolyzing DNA contributing to the junction-specific endonuclease activity observed during DNA repair and recombination events
  • involved in transcription-coupled repair (TCR) of oxidative lesions
  • ERCC1/ERCC4 is a heterodimeric, structure-specific endonuclease that cleaves single-stranded/double-stranded DNA junctions and has roles in nucleotide excision repair (NER), interstrand crosslink (ICL) repair, homologous recombination, and possibly other pathways
  • NER factors ERCC5 and ERCC4 are essential for establishing CTCF-dependent chromatin looping between the promoter and terminator of the activated RARB2 gene
  • ERCC5 endonuclease promotes DNA breaks and DNA demethylation at promoters allowing the recruitment of CTCF and gene looping, which is further stabilized by ERCC4
  • plays an important role in nucleotide excision repair and participates in removal of DNA interstrand cross-links and DNA double-strand breaks
  • DCLRE1C and ERCC4-ERCC1 can also induce stalled DNA replication forks cleavage through non-epistatic pathways all along S and G2 phases of the cell cycle
  • MUS81 and ERCC4 are a subset of Structure-specific endonucleases (SSEs) that resolve aberrant replication structures
  • CELLULAR PROCESS nucleotide, repair, nucleotide excision repair
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    nucleotide-excision repair
    a component
  • structure specific DNA endonuclease complex with ERCC1, ERCC4-ERCC1 is a nuclease that plays a critical role in DNA repair (Ahmad 2010)
  • INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • ERCC1 binding (participating in nucleotide excision repair and homology-dependent recombination reactions, including DNA single strand annealing and gene targeting)
  • RAD52 interacting with XPF/ERCC1 is the active species that processes recombination intermediates generated during the repair of DNA double strand breaks and in homology-dependent gene targeting events
  • collaboration between DCLRE1A and ERCC4-ERCC1 is necessary to initiate ICL repair in replicating human cells
  • ERCC4, ERCC5 are essential for establishing CTCF-dependent chromatin looping between the promoter and terminator of the activated RARB2 gene
  • Rapid Replication Fork Breakage (RRFB) mediated by DCLRE1C and ERCC4 in response to DNA replication stress (DRS) contributes to DNA replication efficiency and limit chromosomal instability
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) XPF , XFEP , FANCQ
    Susceptibility
  • to lung cancer
  • to cutaneous melanoma
  • to squamous cell carcinoma of the head and neck (SCCHN)
  • Variant & Polymorphism other
  • polymorphism rs3136038 on the promotor region of ERCC4 may contribute to the etiology of lung cancer (Shao 2008)
  • significant associations with the strongest associations for melanoma cases aged 50 and under (POvey 2007)
  • two SNPs (rs2276466 and rs3136038) in ERCC4 may be functional and contribute to SCCHN susceptibility
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS