Insights into DNA recombination from the structure of a RAD51-BRCA2 complex

被引：541
作者：
Pellegrini, L
Yu, DS
Lo, T
Anand, S
Lee, M
Blundell, TL
Venkitaraman, AR [1 ]
机构：
[1] Univ Cambridge, CR UK Dept Oncol, Cambridge CB2 2XZ, England
[2] Hutchison MRC Res Ctr, MRC, Canc Cell Unit, Cambridge CB2 2XZ, England
[3] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England
来源：
NATURE | 2002年 / 420卷 / 6913期
基金：
英国惠康基金; 英国医学研究理事会;
关键词：
D O I：
10.1038/nature01230
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：
The breast cancer susceptibility protein BRCA2 controls the function of RAD51, a recombinase enzyme, in pathways for DNA repair by homologous recombination. We report here the structure of a complex between an evolutionarily conserved sequence in BRCA2 ( the BRC repeat) and the RecA-homology domain of RAD51. The BRC repeat mimics a motif in RAD51 that serves as an interface for oligomerization between individual RAD51 monomers, thus enabling BRCA2 to control the assembly of the RAD51 nucleoprotein filament, which is essential for strand-pairing reactions during DNA recombination. The RAD51 oligomerization motif is highly conserved among RecA-like recombinases, highlighting a common evolutionary origin for the mechanism of nucleoprotein filament formation, mirrored in the BRC repeat. Cancer-associated mutations that affect the BRC repeat disrupt its predicted interaction with RAD51, yielding structural insight into mechanisms for cancer susceptibility.
引用
收藏
页码：287 / 293
页数：7
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