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Gene Review

XRCC3  -  X-ray repair complementing defective...

Homo sapiens

Synonyms: DNA repair protein XRCC3, X-ray repair cross-complementing protein 3
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Disease relevance of XRCC3


High impact information on XRCC3

  • XRCC3 possesses a limited sequence similarity to Rad51 and interacts with it [6].
  • Using a novel fluorescence-based assay, we demonstrate here that error-free homology-directed repair of DNA double-strand breaks is decreased 25-fold in an XRCC3-deficient hamster cell line and can be restored to wild-type levels through XRCC3 expression [6].
  • XRCC3 promotes homology-directed repair of DNA damage in mammalian cells [6].
  • XRCC3 mutation causes severe chromosome instability [7].
  • We find that XRCC3 mutant cells display radically altered HR product spectra, with increased gene conversion tract lengths, increased frequencies of discontinuous tracts, and frequent local rearrangements associated with HR [7].

Chemical compound and disease context of XRCC3

  • Cancer occurrence was strongly associated with the XRCC3 Met/Met polymorphic variant (OR = 9.45; (95% CI 8.77-11.65)), whereas Thr/Thr and Thr/Met variants were associated with significant reduction in colorectal cancer risk (OR = 0.16; 95% CI 0-0.26 and OR = 0.26; 95% CI 0.25-0.27, respectively) [8].
  • XRCC1, XRCC3, and XPD Polymorphisms as Modifiers of the Effect of Smoking and Alcohol on Colorectal Adenoma Risk [9].

Biological context of XRCC3

  • XRCC2 and XRCC3, new human Rad51-family members, promote chromosome stability and protect against DNA cross-links and other damages [10].
  • We studied polymorphisms in 3 DNA repair genes: XRCC1, XRCC3, and XPD [11].
  • In the homologous recombination (HR) pathway, genotype frequencies differed between cases and controls for two polymorphisms in XRCC3; T241M (P=0.015) and IVS5 A>G at nt 17893 (P=0.008) [12].
  • For XRCC3, we found evidence for four common haplotypes and four rarer ones that appear to have arisen by recombination [12].
  • The XRCC2, XRCC3, and XRCC5 mutants also showed normal induction kinetics [13].

Anatomical context of XRCC3


Associations of XRCC3 with chemical compounds


Physical interactions of XRCC3


Regulatory relationships of XRCC3


Other interactions of XRCC3


Analytical, diagnostic and therapeutic context of XRCC3


  1. Lack of involvement of nucleotide excision repair gene polymorphisms in colorectal cancer. Mort, R., Mo, L., McEwan, C., Melton, D.W. Br. J. Cancer (2003) [Pubmed]
  2. Xrcc3 is recruited to DNA double strand breaks early and independent of Rad51. Forget, A.L., Bennett, B.T., Knight, K.L. J. Cell. Biochem. (2004) [Pubmed]
  3. Prediction of normal tissue radiosensitivity from polymorphisms in candidate genes. Andreassen, C.N., Alsner, J., Overgaard, M., Overgaard, J. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. (2003) [Pubmed]
  4. DNA repair gene polymorphisms and risk of second primary neoplasms and mortality in oral cancer patients. Gal, T.J., Huang, W.Y., Chen, C., Hayes, R.B., Schwartz, S.M. Laryngoscope (2005) [Pubmed]
  5. DNA-repair genetic polymorphisms and breast cancer risk. Smith, T.R., Levine, E.A., Perrier, N.D., Miller, M.S., Freimanis, R.I., Lohman, K., Case, L.D., Xu, J., Mohrenweiser, H.W., Hu, J.J. Cancer Epidemiol. Biomarkers Prev. (2003) [Pubmed]
  6. XRCC3 promotes homology-directed repair of DNA damage in mammalian cells. Pierce, A.J., Johnson, R.D., Thompson, L.H., Jasin, M. Genes Dev. (1999) [Pubmed]
  7. XRCC3 controls the fidelity of homologous recombination: roles for XRCC3 in late stages of recombination. Brenneman, M.A., Wagener, B.M., Miller, C.A., Allen, C., Nickoloff, J.A. Mol. Cell (2002) [Pubmed]
  8. An association of polymorphism of DNA repair genes XRCC1 and XRCC3 with colorectal cancer. Krupa, R., Blasiak, J. J. Exp. Clin. Cancer Res. (2004) [Pubmed]
  9. XRCC1, XRCC3, and XPD Polymorphisms as Modifiers of the Effect of Smoking and Alcohol on Colorectal Adenoma Risk. Stern, M.C., Siegmund, K.D., Conti, D.V., Corral, R., Haile, R.W. Cancer Epidemiol. Biomarkers Prev. (2006) [Pubmed]
  10. XRCC2 and XRCC3, new human Rad51-family members, promote chromosome stability and protect against DNA cross-links and other damages. Liu, N., Lamerdin, J.E., Tebbs, R.S., Schild, D., Tucker, J.D., Shen, M.R., Brookman, K.W., Siciliano, M.J., Walter, C.A., Fan, W., Narayana, L.S., Zhou, Z.Q., Adamson, A.W., Sorensen, K.J., Chen, D.J., Jones, N.J., Thompson, L.H. Mol. Cell (1998) [Pubmed]
  11. The genotype distribution of the XRCC1 gene indicates a role for base excision repair in the development of therapy-related acute myeloblastic leukemia. Seedhouse, C., Bainton, R., Lewis, M., Harding, A., Russell, N., Das-Gupta, E. Blood (2002) [Pubmed]
  12. Variants in DNA double-strand break repair genes and breast cancer susceptibility. Kuschel, B., Auranen, A., McBride, S., Novik, K.L., Antoniou, A., Lipscombe, J.M., Day, N.E., Easton, D.F., Ponder, B.A., Pharoah, P.D., Dunning, A. Hum. Mol. Genet. (2002) [Pubmed]
  13. Defining the roles of nucleotide excision repair and recombination in the repair of DNA interstrand cross-links in mammalian cells. De Silva, I.U., McHugh, P.J., Clingen, P.H., Hartley, J.A. Mol. Cell. Biol. (2000) [Pubmed]
  14. Human Rad51C deficiency destabilizes XRCC3, impairs recombination, and radiosensitizes S/G2-phase cells. Lio, Y.C., Schild, D., Brenneman, M.A., Redpath, J.L., Chen, D.J. J. Biol. Chem. (2004) [Pubmed]
  15. Genetic interactions between RAD51 and its paralogues for centrosome fragmentation and ploidy control, independently of the sensitivity to genotoxic stresses. Daboussi, F., Thacker, J., Lopez, B.S. Oncogene (2005) [Pubmed]
  16. A naturally occurring genetic variant of human XRCC2 (R188H) confers increased resistance to cisplatin-induced DNA damage. Danoy, P., Sonoda, E., Lathrop, M., Takeda, S., Matsuda, F. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  17. Homologous recombination as a potential target for caffeine radiosensitization in mammalian cells: reduced caffeine radiosensitization in XRCC2 and XRCC3 mutants. Asaad, N.A., Zeng, Z.C., Guan, J., Thacker, J., Iliakis, G. Oncogene (2000) [Pubmed]
  18. Polymorphisms in DNA repair genes as risk factors for spina bifida and orofacial clefts. Olshan, A.F., Shaw, G.M., Millikan, R.C., Laurent, C., Finnell, R.H. Am. J. Med. Genet. A (2005) [Pubmed]
  19. XRCC1 and XRCC3 polymorphisms and their role as effect modifiers of unsaturated fatty acids and antioxidant intake on colorectal adenomas risk. Stern, M.C., Siegmund, K.D., Corral, R., Haile, R.W. Cancer Epidemiol. Biomarkers Prev. (2005) [Pubmed]
  20. Polymorphisms in DNA repair genes modulate survival in cisplatin/gemcitabine-treated non-small-cell lung cancer patients. de Las Peñas, R., Sanchez-Ronco, M., Alberola, V., Taron, M., Camps, C., Garcia-Carbonero, R., Massuti, B., Queralt, C., Botia, M., Garcia-Gomez, R., Isla, D., Cobo, M., Santarpia, M., Cecere, F., Mendez, P., Sanchez, J.J., Rosell, R. Ann. Oncol. (2006) [Pubmed]
  21. DNA repair gene XRCC3 codon 241 polymorphism, its interaction with smoking and XRCC1 polymorphisms, and bladder cancer risk. Stern, M.C., Umbach, D.M., Lunn, R.M., Taylor, J.A. Cancer Epidemiol. Biomarkers Prev. (2002) [Pubmed]
  22. Evidence for simultaneous protein interactions between human Rad51 paralogs. Schild, D., Lio, Y.C., Collins, D.W., Tsomondo, T., Chen, D.J. J. Biol. Chem. (2000) [Pubmed]
  23. DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder cancer in a case-control study. Matullo, G., Guarrera, S., Carturan, S., Peluso, M., Malaveille, C., Davico, L., Piazza, A., Vineis, P. Int. J. Cancer (2001) [Pubmed]
  24. Tetratricopeptide-motif-mediated interaction of FANCG with recombination proteins XRCC3 and BRCA2. Hussain, S., Wilson, J.B., Blom, E., Thompson, L.H., Sung, P., Gordon, S.M., Kupfer, G.M., Joenje, H., Mathew, C.G., Jones, N.J. DNA Repair (Amst.) (2006) [Pubmed]
  25. XRCC3 depletion induces spontaneous DNA breaks and p53-dependent cell death. Loignon, M., Amrein, L., Dunn, M., Aloyz, R. Cell Cycle (2007) [Pubmed]
  26. Interplay between human DNA repair proteins at a unique double-strand break in vivo. Rodrigue, A., Lafrance, M., Gauthier, M.C., McDonald, D., Hendzel, M., West, S.C., Jasin, M., Masson, J.Y. EMBO J. (2006) [Pubmed]
  27. Complex formation by the human RAD51C and XRCC3 recombination repair proteins. Masson, J.Y., Stasiak, A.Z., Stasiak, A., Benson, F.E., West, S.C. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  28. Polymorphisms of phase II xenobiotic-metabolizing and DNA repair genes and in vitro N-ethyl-N-nitrosourea-induced O(6)-ethylguanine levels in human lymphocytes. Jiao, L., Chang, P., Firozi, P.F., Lai, D., Abbruzzese, J.L., Li, D. Mutat. Res. (2007) [Pubmed]
  29. Rare microsatellite polymorphisms in the DNA repair genes XRCC1, XRCC3 and XRCC5 associated with cancer in patients of varying radiosensitivity. Price, E.A., Bourne, S.L., Radbourne, R., Lawton, P.A., Lamerdin, J., Thompson, L.H., Arrand, J.E. Somat. Cell Mol. Genet. (1997) [Pubmed]
  30. XRCC3 ATPase activity is required for normal XRCC3-Rad51C complex dynamics and homologous recombination. Yamada, N.A., Hinz, J.M., Kopf, V.L., Segalle, K.D., Thompson, L.H. J. Biol. Chem. (2004) [Pubmed]
  31. Role of RAD51C and XRCC3 in genetic recombination and DNA repair. Liu, Y., Tarsounas, M., O'regan, P., West, S.C. J. Biol. Chem. (2007) [Pubmed]
  32. Polymorphisms of the XRCC1, XRCC3, & XPD genes, and colorectal cancer risk: a case-control study in Taiwan. Yeh, C.C., Sung, F.C., Tang, R., Chang-Chieh, C.R., Hsieh, L.L. BMC Cancer (2005) [Pubmed]
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