| Literature DB >> 28976962 |
Weixing Zhao1, Justin B Steinfeld2, Fengshan Liang1,3,4, Xiaoyong Chen3,4, David G Maranon5, Chu Jian Ma2, Youngho Kwon1, Timsi Rao1, Weibin Wang1, Chen Sheng1, Xuemei Song6, Yanhong Deng6, Judit Jimenez-Sainz7, Lucy Lu1, Ryan B Jensen7, Yong Xiong1, Gary M Kupfer3,4, Claudia Wiese5, Eric C Greene2, Patrick Sung1,7.
Abstract
The tumour suppressor complex BRCA1-BARD1 functions in the repair of DNA double-stranded breaks by homologous recombination. During this process, BRCA1-BARD1 facilitates the nucleolytic resection of DNA ends to generate a single-stranded template for the recruitment of another tumour suppressor complex, BRCA2-PALB2, and the recombinase RAD51. Here, by examining purified wild-type and mutant BRCA1-BARD1, we show that both BRCA1 and BARD1 bind DNA and interact with RAD51, and that BRCA1-BARD1 enhances the recombinase activity of RAD51. Mechanistically, BRCA1-BARD1 promotes the assembly of the synaptic complex, an essential intermediate in RAD51-mediated DNA joint formation. We provide evidence that BRCA1 and BARD1 are indispensable for RAD51 stimulation. Notably, BRCA1-BARD1 mutants with weakened RAD51 interactions show compromised DNA joint formation and impaired mediation of homologous recombination and DNA repair in cells. Our results identify a late role of BRCA1-BARD1 in homologous recombination, an attribute of the tumour suppressor complex that could be targeted in cancer therapy.Entities:
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Year: 2017 PMID： 28976962 PMCID： PMC5800781 DOI： 10.1038/nature24060
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962