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FLASH GENE
Symbol XRCC3 contributors: mct/npt/pgu - updated : 28-11-2023
HGNC name X-ray repair complementing defective repair in Chinese hamster cells 3
HGNC id 12830
DNA
TYPE functioning gene
STRUCTURE 17.83 kb     9 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
text structure
  • INO80 binds to the promoters of the RAD54B and XRCC3 genes
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 2563 - 346 - 1999 10541549
    10 - 2657 - 346 - 1999 10541549
    10 - 2620 - 346 - 1999 10541549
    10 - 2661 - 346 - 1999 10541549
    10 - 2577 - 346 - 1999 10541549
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
     mouth   highly
    Endocrinepancreas    
    Lymphoid/Immunetonsils   highly
    Reproductivemale systemprostate   
     male systemtestis   
    Visualeyelens   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two ATP binding domain (Walker B box A and B)
  • HOMOLOGY
    intraspecies paralog to RAD51
    paralog to RAD51C
    Homologene
    FAMILY
  • RECA family
  • RAD51 subfamily
  • CATEGORY DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nuclear envelope
    basic FUNCTION
  • involved in the recombination repair pathway, of double-stranded DNA
  • play an important role in the repair of DNA double-strand breaks (DSBs) by homologous recombination
  • RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3, play an essential role in the DNA repair reactions through homologous recombination
  • RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3 are key enzymes for DNA double-strand break repair
  • functions jointly with GEN1 later in the pathway at the stage of Holliday junction resolution
  • XRCC2 and XRCC3 complexes act at different stages of the homologous recombination (HR) pathway
  • XRCC3 and RAD51C have been implicated in homologous recombination (HR) and DNA damage responses
  • XRCC3 is a new player in the ATM/ATR-induced DNA damage responses to control checkpoint and HR-mediated repair
  • plays an important role in the repair of DNA double-strand breaks
  • likely a direct role of RAD51C/XRCC3 in maintaining mtDNA integrity under replication stress conditions
  • RAD51B, RAD51C, RAD51D, XRCC2, XRCC3 sequentially orchestrate clinically relevant transactions at replication forks, cooperatively promoting fork remodeling and restart
  • function of XRCC3 and other RAD51 paralogs in synergizing with RAD51 nucleoprotein filament to prevent degradation of stressed replication forks
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    pathway in cells for the repair of severe DNA damage such as double-strand breaks
    a component
  • RAD51C-XRCC3 complex may function in a manner that is distinct from other RAD51 paralogs by playing a specific role in the resolution of recombination intermediates prior to chromosome segregation
  • RAD51C/XRCC3 is an additional component of the mitochondrial nucleoid having nucleus-independent roles in mtDNA maintenance
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • RAD51, RAD51C
  • interacting with BLM (disruption of XRCC3 suppresses MMS and UV sensitivity and the methyl methanesulfonate- and UV-induced chromosomal aberrations of BLM cells, indicating that BLM acts downstream of XRCC3)
  • interacting with RAD54B genes
  • interacting with INO80 (binds to the promoters of the RAD54B and XRCC3 genes)
  • cell & other
    REGULATION
    Other regulated by FANCC (regulates XRCC3, telomere-binding proteins or histone methyltransferases in telomere recombination)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    resulting in a defect in recombination and increased endoreduplication in cells , having a role in cancer susceptibility
    constitutional     --low  
    results in a dramatic decrease in mtDNA copy number as well as the complete suppression of a characteristic oxidative stress-induced copy number increase
    tumoral germinal mutation      
    germinal deleterious variants in the RAD51 paralogs to breast and ovarian cancers
    Susceptibility
  • to myeloma for some htSNPs
  • to malignant melanoma, breast cancer,
  • to squamous cell carcinoma of head and neck
  • to colorectal cancer
  • to lung and colorectal cancer
  • to ovarian cancer risk
  • to late adverse effects induced by radiotherapy
  • Variant & Polymorphism
  • T241-M in breast cancer and melanoma
  • 241Met allele may be an effective biomarker for genetic susceptibility to colorectal cancer
  • XRCC3 241Met allele was associated with an increased risk of lung and colorectal cancer
  • XRCC3 rs1799794 polymorphisms, having a statistically significant correlation with ovarian cancer risk
  • XRCC3 rs1799794 polymorphism may have a protective effect against late adverse effects induced by radiotherapy
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Xrcc3 knockout mice exhibit midgestational lethality, with mild phenotypes beginning at about E8.25 but severe developmental abnormalities evident by E9.0-9.5