A new protein complex promoting the assembly of Rad51 filaments

被引:81
作者
Sasanuma, Hiroyuki [1 ]
Tawaramoto, Maki S. [1 ]
Lao, Jessica P. [2 ,3 ,4 ]
Hosaka, Harumi [1 ]
Sanda, Eri [1 ]
Suzuki, Mamoru [1 ]
Yamashita, Eiki [1 ]
Hunter, Neil [2 ,3 ,4 ]
Shinohara, Miki [1 ]
Nakagawa, Atsushi [1 ]
Shinohara, Akira [1 ]
机构
[1] Osaka Univ, Grad Sch Sci, Inst Prot Res, Suita, Osaka 5650871, Japan
[2] Univ Calif Davis, Howard Hughes Med Inst, Dept Microbiol & Mol Genet, Davis, CA 95616 USA
[3] Univ Calif Davis, Howard Hughes Med Inst, Dept Mol & Cellular Biol, Davis, CA 95616 USA
[4] Univ Calif Davis, Howard Hughes Med Inst, Dept Cell Biol & Human Anat, Davis, CA 95616 USA
基金
日本学术振兴会;
关键词
DOUBLE-STRAND BREAK; SACCHAROMYCES-CEREVISIAE; MEIOTIC RECOMBINATION; SHU-COMPLEX; HOMOLOGOUS RECOMBINATION; REPAIR; GENES; DMC1; MEIOSIS; SCREEN;
D O I
10.1038/ncomms2678
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
During homologous recombination, eukaryotic RecA homologue Rad51 assembles into a nucleoprotein filament on single-stranded DNA to catalyse homologous pairing and DNA-strand exchange with a homologous template. Rad51 nucleoprotein filaments are highly dynamic and regulated via the coordinated actions of various accessory proteins including Rad51 mediators. Here, we identify a new Rad51 mediator complex. The PCSS complex, comprising budding yeast Psy3, Csm2, Shu1 and Shu2 proteins, binds to recombination sites and is required for Rad51 assembly and function during meiosis. Within the hetero-tetramer, Psy3-Csm2 constitutes a core sub-complex with DNA-binding activity. In vitro, purified Psy3-Csm2 stabilizes the Rad51-single-stranded DNA complex independently of nucleotide cofactor. The mechanism of Rad51 stabilization is inferred by our high-resolution crystal structure, which reveals Psy3-Csm2 to be a structural mimic of the Rad51-dimer, a fundamental unit of the Rad51-filament. Together, these results reveal a novel molecular mechanism for this class of Rad51-mediators, which includes the human Rad51 paralogues.
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页数:13
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