title: The epistatic relationship between BRCA2 and the other RAD51 mediators in homologous recombination.
abstract: RAD51 recombinase polymerizes at the site of double-strand breaks (DSBs) where it performs DSB repair. The loss of RAD51 causes extensive chromosomal breaks, leading to apoptosis. The polymerization of RAD51 is regulated by a number of RAD51 mediators, such as BRCA1, BRCA2, RAD52, SFR1, SWS1, and the five RAD51 paralogs, including XRCC3. We here show that brca2-null mutant cells were able to proliferate, indicating that RAD51 can perform DSB repair in the absence of BRCA2. We disrupted the BRCA1, RAD52, SFR1, SWS1, and XRCC3 genes in the brca2-null cells. All the resulting double-mutant cells displayed a phenotype that was very similar to that of the brca2-null cells. We suggest that BRCA2 might thus serve as a platform to recruit various RAD51 mediators at the appropriate position at the DNA-damage site.
authors.affiliation: Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yong
authors.initials: Y
authors.lastname: Qing
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Yamazoe
authors.forename: Kouji
authors.initials: K
authors.lastname: Hirota
authors.forename: Donniphat
authors.initials: D
authors.lastname: Dejsuphong
authors.forename: Wataru
authors.initials: W
authors.lastname: Sakai
authors.forename: Kimiyo N
authors.initials: KN
authors.lastname: Yamamoto
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Bishop
authors.forename: XiaoHua
authors.initials: X
authors.lastname: Wu
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takeda
mesh_terms: D000818:Animals; D024682:BRCA2 Protein / Q000235:genetics*; D002166:Camptothecin / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002645:Chickens; D002869:Chromosome Aberrations / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000494:pharmacology; D002999:Clone Cells; D004249:DNA Damage; D004843:Epistasis, Genetic / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D005785:Gene Conversion / Q000187:drug effects / Q000528:radiation effects; D017353:Gene Deletion; D056426:Genetic Loci / Q000235:genetics; D016678:Genome / Q000235:genetics; D059765:Homologous Recombination / Q000187:drug effects / Q000528:radiation effects; D008954:Models, Biological; D010641:Phenotype; D010793:Phthalazines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051135:Rad51 Recombinase / Q000172:deficiency / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D010793:Phthalazines; D010879:Piperazines; D051135:Rad51 Recombinase; D002945:Cisplatin; C531550:olaparib; D002166:Camptothecin