XRCC3 (X-ray repair complementing defective repair in Chinese hamster cells 3)

2005-11-01   Ulla Vogel 

National Research Centre for the Working Environment, Lersø Parkalle 105, DK-2100 Copenhagen O, Denmark





17 800 bp, 9 exons


2,504 bp



346 amino acids


XRCC3 is required for efficient repair of double strand breaks via homologous recombinational repair (link), for correct chromosomal segregation and for repair of DNA cross links. Inactivation of XRCC3 in CHO cells results in increased radiation and cisplatin sensitivity. In human cells, XRCC3 forms a complex with Rad51C which is recruited early to DNA damage. Inactivation of XRCC3 in human cells leads to a two-fold sensitivity to DNA cross-linking agents, impaired Rad51 focus formation, elevated chromosome aberrations and five to seven-fold increased endoreduplication.


XRCC3 is a paralog to rad51

Implicated in

Entity name
No human disease has been linked to inactivation of XRCC3. However, polymorphisms in XRCC3 may be associated with increased cancer risk (see below).
Genetic Epidemiology:
The most frequent polymorphism in XRCC3 is XRCC3 C18067T which results in a Thr to Met amino acid substitution at codon 241. Carriers of the variant T-allele of XRCC3 T241M have higher DNA adduct levels in lymphocyte DNA compared to homozygous C-allele carriers, indicating that the polymorphism is associated with lowered DNA repair capacity. The variant allele of XRCC3 T241M polymorphism has been associated with increased risk of squamous cell carcinoma of the head and neck in one study while another study found no association. No association has previously been found with colon cancer, non-melanoma skin cancer, prostate cancer, gastric cancer, ovarian cancer. Conflicting results have been published on the association with breast cancer, bladder cancer, malignant melanoma and lung cancer.
Two frequent SNP are upstream of XRCC3 T241M have also been studied, namely XRCC3 A4541G and XRCC3 A17897G. Neither polymorphism gives rise to amino acid changes. The variant allele of A17897G has been associated with decreased risk of breast cancer and ovarian cancer. The same tendency, but no significant associations was found for lung cancer.
XRCC3 A4541G was not associated to risk of breast cancer or lung cancer. However, homozygote carriers of the variant allele had lower risk of serous epithelial ovarian cancer.


Pubmed IDLast YearTitleAuthors
159243372005Polymorphisms in DNA repair genes and epithelial ovarian cancer risk.Auranen A et al
114897612001No association between the XPD (Lys751G1n) polymorphism or the XRCC3 (Thr241Met) polymorphism and lung cancer risk.David-Beabes GL et al
123765262002DNA repair gene XRCC3 241Met variant is not associated with risk of cutaneous malignant melanoma.Duan Z et al
159142102005Basal cell carcinoma and variants in genes coding for immune response, DNA repair, folate and iron metabolism.Festa F et al
153726202004Xrcc3 is recruited to DNA double strand breaks early and independent of Rad51.Forget AL et al
110256692000Mammalian recombination-repair genes XRCC2 and XRCC3 promote correct chromosome segregation.Griffin CS et al
145781642004Polymorphisms in DNA double-strand break repair genes and breast cancer risk in the Nurses' Health Study.Han J et al
158022982005Selected DNA repair polymorphisms and gastric cancer in Poland.Huang WY et al
160301122005Selected genetic polymorphisms in MGMT, XRCC1, XPD, and XRCC3 and risk of head and neck cancer: a pooled analysis.Huang WY et al
153126852004XRCC3 polymorphisms and risk of lung cancer.Jacobsen NR et al
120239822002Variants in DNA double-strand break repair genes and breast cancer susceptibility.Kuschel B et al
96609621998XRCC2 and XRCC3, new human Rad51-family members, promote chromosome stability and protect against DNA cross-links and other damages.Liu N et al
113046922001DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder cancer in a case-control study.Matullo G et al
115328662001XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects.Matullo G et al
128659262003Lack of involvement of nucleotide excision repair gene polymorphisms in colorectal cancer.Mort R et al
153334652004Specific combinations of DNA repair gene variants and increased risk for non-small cell lung cancer.Popanda O et al
158165182005A comparison of response to cisplatin, radiation and combined treatment for cells deficient in recombination repair pathways.Raaphorst GP et al
160301052005Genetic variants of DNA repair genes and prostate cancer: a population-based study.Ritchey JD et al
146880162004Polymorphisms in DNA repair and metabolic genes in bladder cancer.Sanyal S et al
121154902002A variant of the DNA repair gene XRCC3 and risk of squamous cell carcinoma of the head and neck: a case-control analysis.Shen H et al
146522872003Polymorphisms of the DNA repair genes XRCC1, XRCC3, XPD, interaction with environmental exposures, and bladder cancer risk in a case-control study in northern Italy.Shen M et al
125651732003Polymorphisms of XRCC1 and XRCC3 genes and susceptibility to breast cancer.Smith TR et al
122234432002DNA repair gene XRCC3 codon 241 polymorphism, its interaction with smoking and XRCC1 polymorphisms, and bladder cancer risk.Stern MC et al
157349522005Double-strand break repair gene polymorphisms and risk of breast or ovarian cancer.Webb PM et al
110597482000A variant within the DNA repair gene XRCC3 is associated with the development of melanoma skin cancer.Winsey SL et al
156798832005Polymorphisms of the XRCC1, XRCC3, & XPD genes, and colorectal cancer risk: a case-control study in Taiwan.Yeh CC et al
147497352004XRCC3 deficiency results in a defect in recombination and increased endoreduplication in human cells.Yoshihara T et al

Other Information

Locus ID:

NCBI: 7517
MIM: 600675
HGNC: 12830
Ensembl: ENSG00000126215


dbSNP: 7517
ClinVar: 7517
TCGA: ENSG00000126215


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Homologous recombinationKEGGko03440
Homologous recombinationKEGGhsa03440
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 Homologous Recombination (HRR)REACTOMER-HSA-5685942
Homologous DNA Pairing and Strand ExchangeREACTOMER-HSA-5693579
Resolution of D-Loop StructuresREACTOMER-HSA-5693537
Resolution of D-loop Structures through Holliday Junction IntermediatesREACTOMER-HSA-5693568
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)REACTOMER-HSA-5693554


Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA164713176Platinum compoundsChemicalClinicalAnnotationassociatedPD23940523, 27248474
PA443622Carcinoma, Non-Small-Cell LungDiseaseClinicalAnnotationassociatedPD23940523, 27248474
PA446108Colorectal NeoplasmsDiseaseClinicalAnnotationassociatedPD17549067


Pubmed IDYearTitleCitations
105415491999XRCC3 promotes homology-directed repair of DNA damage in mammalian cells.550
161952372006Polymorphisms of DNA repair genes and risk of non-small cell lung cancer.112
115328662001XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects.91
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
157461602005Constitutional short telomeres are strong genetic susceptibility markers for bladder cancer.83
170187852006Commonly studied single-nucleotide polymorphisms and breast cancer: results from the Breast Cancer Association Consortium.83
174010132007Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFOX-4 chemotherapy.77
120239822002Variants in DNA double-strand break repair genes and breast cancer susceptibility.74
166090222006Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer.71
187014352008Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk.63


Ulla Vogel

XRCC3 (X-ray repair complementing defective repair in Chinese hamster cells 3)

Atlas Genet Cytogenet Oncol Haematol. 2005-11-01

Online version: http://atlasgeneticsoncology.org/gene/335/xrcc3-(x-ray-repair-complementing-defective-repair-in-chinese-hamster-cells-3)