Xrcc3 is recruited to DNA double strand breaks early and independent of Rad51
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyGraduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2004-09-17Keywords
Animals; CHO Cells; Cells, Cultured; Cricetinae; Cricetulus; DNA Damage; DNA Repair; DNA-Binding Proteins; Gamma Rays; Humans; RNA, Small Interfering; Rad51 Recombinase; *Recombination, GeneticLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Rad51-mediated homologous recombination (HR) is essential for maintenance of genome integrity. The Xrcc3 protein functions in HR DNA repair, and studies suggest it has multiple roles at different stages in this pathway. Defects in vertebrate XRCC3 result in elevated levels of spontaneous and DNA damage-induced chromosomal abnormalities, as well as increased sensitivity to DNA damaging agents. Formation of DNA damaged-induced nuclear Rad51 foci requires Xrcc3 and the other Rad51 paralog proteins (Rad51B, Rad51C, Rad51D, Xrcc2), thus supporting a model in which an early function of Xrcc3 involves promoting assembly of active Rad51 repair complexes. However, it is not known whether Xrcc3 or other Rad51 paralog proteins accumulate at DNA breaks, and if they do whether their stable association with breaks requires Rad51. Here we report for the first time that Xrcc3 forms distinct foci in human cells and that nuclear Xrcc3 begins to localize at sites of DNA damage within 10 min after radiation treatment. RNAi-mediated knock down of Rad51 has no effect on the DNA damage-induced localization of Xrcc3 to DNA breaks. Our data are consistent with a model in which Xrcc3 associates directly with DNA breaks independent of Rad51, and subsequently facilitates formation of the Rad51 nucleoprotein filament.Source
J Cell Biochem. 2004 Oct 15;93(3):429-36. Link to article on publisher's siteDOI
10.1002/jcb.20232Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33627PubMed ID
15372620Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1002/jcb.20232