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FLASH GENE
Symbol XRCC1 contributors: shn/npt/pgu - updated : 19-10-2018
HGNC name X-ray repair complementing defective repair in Chinese hamster cells 1
HGNC id 12828
Corresponding disease
SCAR26 Spinocerebellar ataxia, autosomal recessive 26
Location 19q13.31      Physical location : 44.047.463 - 44.079.730
Synonym name
  • repair X-ray defect,complementing defect in CHO cells 1
  • X-ray repair cross complementing 1
  • Synonym symbol(s) RCC
    DNA
    TYPE functioning gene
    STRUCTURE 32.27 kb     17 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site   transcription factor
    text structure transcription factor E2F1 binds to the XRCC1 promoter region and regulates XRCC1 transcription
    MAPPING cloned Y linked N status confirmed
    Map cen - D19S537 - D19S408 - XRCC1 - D19S900 - D19S913 - qter
    Physical map
    PSG11 19q13.2 pregnancy specific beta-1-glycoprotein 11 CEACAMP8 19q13.2 carcinoembryonic antigen-related cell adhesion molecule pseudogene 8 PSG2 19q13.2 pregnancy specific beta-1-glycoprotein 2 CEACAMP9 19q13.2 carcinoembryonic antigen-related cell adhesion molecule pseudogene 9 PSG5 19q13.2 pregnancy specific beta-1-glycoprotein 5 PSG4 19q13.2 pregnancy specific beta-1-glycoprotein 4 CEACAMP10 19q13.2 carcinoembryonic antigen-related cell adhesion molecule pseudogene 10 PSG9 19q13.2 pregnancy specific beta-1-glycoprotein 9 CEACAMP11 19q13.2 carcinoembryonic antigen-related cell adhesion molecule pseudogene 11 CEACAMP4 19q13.2 carcinoembryonic antigen-related cell adhesion molecule pseudogene 4 PRV1 19q13.2 carcinoembryonic antigen-related cell adhesion molecule pseudogene 4 LOC388547 19 similar to polycythemia rubra vera 1; cell surface receptor MGC4766 19q13.32 testis-specific protein TES101RP C4.4A 19q13.32 GPI-anchored metastasis-associated protein homolog LOC388548 19 similar to LL5 beta LOC284345 19q13.32 similar to LL5 beta ETHE1 LOC284346 19q13.32 hypothetical protein LOC284346 XRCC1 19q13.2 X-ray repair complementing defective repair in Chinese hamster cells 1 LOC390940 19 similar to R28379_1 LOC126298 19q13.32 similar to FKSG27 MGC2508 19q13.32 hypothetical protein MGC2508 MGC51082 19q13.32 hypothetical protein MGC51082 TSLL2 19q13.32 hypothetical protein MGC51082 PLAUR 19q13.2 plasminogen activator, urokinase receptor R30953_1 19q13.32 hypothetical protein R30953_1 FLJ12886 19q13.32 hypothetical protein FLJ12886 KCNN4 19q13.2 potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4 FLJ30469 19q13.32 hypothetical protein FLJ30469 ZNF283 19q13.32 zinc finger protein 283 ZNF404 19q13.32 zinc finger protein 404 ZNF45 19q13.2 zinc finger protein 45 (a Kruppel-associated box (KRAB) domain polypeptide) ZNF221 19q13.2 zinc finger protein 221 ZNF155 19q13.2-q13.32 zinc finger protein 155 (pHZ-96) ZNF230 19q13.2 zinc finger protein 230 ZNF222 19q13.2 zinc finger protein 222 ZNF223 19q13.2 zinc finger protein 223
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 2102 69.3 633 - -
    EXPRESSION
    Type widely
    constitutive of
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain    
    Reproductivefemale systemuteruscervix highly
    Respiratorylung    
    Skin/Tegumentskin   highly
    Visualeye   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal domain (NTD) able to adopt a redox-dependent alternate fold, characterized by a disulfide bond, and binds to POLB
  • a BRCT adaptor domain (BRCA1 C-terminus)
  • two BRCT domains (BRCT1 and BRCT2) mediating a network of protein-protein interactions with several key factors of the DNA single-strand breaks (SSBs) and base damage repair pathways
  • highly conserved REV1-interacting region (RIR) motif
  • mono polymer monomer
    HOMOLOGY
    interspecies ortholog to XRCC1, Pan troglodytes
    ortholog to Xrcc1, Mus musculus
    ortholog to XRCC1, Rattus norvegicus
    Homologene
    FAMILY
    CATEGORY DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus
    basic FUNCTION
  • activator of PNKP and DNA ligase III, involved in single-strand DNA break rejoining
  • may be facilitating DNA strand break and base excision repair
  • involved in the maintenance of genome stability
  • having discrete G1 and S phase-specific functions
  • together with APTX and PARP1, plays an essential role in single-strand DNA break repair
  • required for efficient DNA single-strand breaks repair and genomic stability in human cells
  • stimulates PNKP activity by displacing PNKP from the phosphorylated DNA product
  • involved in the repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents
  • critical scaffold protein that promotes efficient single-strand break repair by coordinating the enzymatic processing of nonconventional 3' or 5' DNA termini and single-strand break gaps
  • protects against the lethality of induced oxidative DNA damage in nondividing neural cells
  • recruiting ARL6IP5 to the DNA damage sites, that mediate the repair of DNA damage induced by oxidative stress via activating the expression of XRCC1 through MAPK-E2F1 signaling pathway and protecting XRCC1 from ubiquitin-proteasome degradation
  • required for neurogenesis of cerebellar interneurons and for hippocampal homeostasis and prevention of neural DNA damage
  • a crucial role in DNA repair pathway during the genesis of the nervous system and highlight cerebellar interneurons
  • can stimulate PNKP by two independent mechanisms (stimulatory effect of phosphorylated XRCC1 on PNKP can be totally inhibited by the presence of excess FHA domain polypeptide, but non-phosphorylated XRCC1 is not susceptible to competition by the FHA domain)
  • plays a central role in base excision repair (BER) and single strand break repair, coordinating the binding and activities of enzymes involved in the repair process
  • functional role of XRCC1 in replication associated BER of uracil
  • XRCC1, a LIG3-stabilizing cofactor, and LIG3 itself have been very widely assumed to provide major end-ligation functions in A-EJ (alternative end-joining)
  • is dispensable for A-EJ during class switch recombination (CSR)
  • possible involvement of XRCC1 and its associated repair factors in post replication repair
  • has no inherent enzymatic activity, and is believed to function in base excision repair as a dedicated scaffold component that coordinates other DNA repair factors
  • is without catalytic activity, but can interact with a number of known repair proteins
  • key factor in single-strand break and base excision repair, is recruited into nuclear bodies formed in response to replication-related single-strand breaks
  • CELLULAR PROCESS nucleotide, repair, base excision repair
    PHYSIOLOGICAL PROCESS nervous system
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA exhibits preferential binding to DNA with single-strand breaks with a gap size of <5 nucleotides
    RNA
    small molecule
    protein
  • polymerase (DNA directed)beta, POLB (
  • DNA ligase III, LIG3 (
  • poly (ADP-ribose) polymerase 1 , PARP1 (
  • double-strand break (DSB) repair heterotrimeric complex DNA-PK in response to ionizing radiation provides the first evidence for their involvement in a common DSB repair pathway
  • DNA POLB
  • Poly(ADP-ribose) polymerase, PARP
  • APEX nuclease (multifunctional DNA repair enzyme) 1, APEX1 (
  • polynucleotide kinase phosphatase, PNKP
  • BRCA1 carboxy terminal (
  • Poly(ADP-ribose) polymerase-2, PARP2 (
  • 8-oxoguanine DNA glycosylase, OGG1
  • Aprataxin, APTX (
  • proliferating cell nuclear antigen, PCNA (
  • DNA ligase 3 (DNL3), polynucleotide kinase 3'-phosphatase, and polymerase beta, ataxia with oculomotor apraxia type 1 (AOA) gene product aprataxin (
  • Condensin I (
  • tyrosyl-DNA phosphodiesterase 1, TDP1
  • aprataxin and PNKP like factor, APLF (
  • ADP-ribosylation-like factor 6 interacting protein 5, ARL6IP5 (may be required for XRCC1 stability)
  • primase, DNA, polypeptide 2 (58kDa), PRIM2
  • directly interacts with the nuclear localization signal-region (NLS) of XRCC1
  • interaction of the XRCC1-derived peptide with REV1 C-terminal domain characterized by dissociation constants in the low micromolar range
  • DNA repair partners of TDP1 include PARP1, XRCC1, ligase III and PNKP from the base excision repair (BER) pathway
  • in response to cellular proliferation and DNA damage, proteasome and HSP90AA1-mediated regulation of POLB and XRCC1 alters the DNA repair complex architecture
  • chromatin remodeling factor SMARCA5 is a novel binding partner of XRCC1, with their interaction dependent on the casein kinase 2-mediated constitutive phosphorylation of XRCC1
  • XRCC1 recruitment is promoted by PARP1, an enzyme that is activated following DNA damage and synthesizes ADP-ribose polymers that XRCC1 binds directly
  • overlapping roles for PARP1 and PARP2 in the recruitment of endogenous XRCC1 and PNKP into oxidized chromatin
  • interacts with multiple enzymes involved in DNA base excision repair and single-strand break repair (SSBR) and is important for genetic integrity and normal neurological function
  • XRCC1 and PNKP interact via a high-affinity phosphorylation-dependent interaction site in XRCC1 and a forkhead-associated domain in PNKP
  • repair function of PNKP is facilitated by its binding to the scaffold protein XRCC1, and phosphorylation of XRCC1 by CSNK2A2 at several consensus sites enables PNKP binding and recruitment to DNA damage
  • XRCC1 phosphorylation affects aprataxin recruitment and DNA deadenylation activity
  • cell & other
    REGULATION
    Other phosphorylated by CHK2 and facilitating recruitment of downstream BER proteins to the initial damage recognition/excision step to promote Base Excision Repair
    regulated by ARL6IP5 under oxidative stress conditions
    ASSOCIATED DISORDERS
    corresponding disease(s) SCAR26
    Susceptibility
  • to squamous cell carcinoma of the head and neck and for tabacco and age related DNA damage
  • to gastric cancer
  • to breast cancer
  • to glioma
  • to testicular germ cell tumors
  • to development of childhood ALL
  • to systemic lupus erythematosus (SLE)
  • Variant & Polymorphism SNP , other
  • A194T increasing the risk of squamous cell carcinoma of the head and neck
  • haplotype D (194Arg, 280Arg, and 399Arg alleles) is a risk type for gastric cancer
  • polymorphisms at the codon 194 and 399 increasing the risk of breast cancer
  • polymorphisms associated with the susceptibility and chromosomal aberration of testicular germ cell tumors
  • may be associated with the progression of primary open-angle glaucoma in male patients of Pakistani origin (
  • EPHX1 Tyr113His polymorphism together with DNA protein XRCC1 Arg399Gln variant known for its deficient DNA repair capacity would represent more prominent risk factors for the development of childhood ALL
  • XRCC1 Arg399Gln polymorphism might be associated with genetic susceptibility to SLE
  • XRCC1 399Gln and 194Trp variants increase glioma risk
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Xrcc1 null mice are morphologically abnormal (increased cell death in the epiblast and an altered morphology in the visceral embryonic endoderm) and die around embryonic day 7
  • mice with neural-specific inactivation of Xrcc1 exhibit profound neuropathology characterized by loss of cerebellar interneurons and persistence of DNA strand breaks throughout the nervous system and abnormal hippocampal function