Role of BRCA2 in control of the RAD51 recombination and DNA repair protein
Role of BRCA2 in control of the RAD51 recombination and DNA repair protein
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DOI：
10.1016/s1097-2765(01)00175-7
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发表时间：
2001-02-01
期刊：
影响因子：
16
通讯作者：
West, SC
中科院分区：
文献类型：
--
作者：
Davies, AA;Masson, JY;West, SC
携带BRCA2突变的个体易患乳腺癌和卵巢癌。在此，我们表明BRCA2在调节RAD51的作用方面起着双重作用，RAD51是一种对同源重组和DNA修复至关重要的蛋白质。首先，RAD51与BRCA2的BRC3或BRC4区域之间的相互作用阻止了RAD51形成核蛋白丝。对BRC3区域进行的模拟癌症相关BRCA2突变的改变未能显示出这种效应。其次，在携带癌症相关BRCA2截断的细胞中，RAD51向细胞核的运输存在缺陷。因此，BRCA2既调节RAD51的细胞内定位，也调节其DNA结合能力。BRCA2失活后这些调控的丧失可能是导致基因组不稳定和肿瘤发生的关键事件。
Individuals carrying BRCA2 mutations are predisposed to breast and ovarian cancers. Here, we show that BRCA2 plays a dual role in regulating the actions of RAD51, a protein essential for homologous recombination and DNA repair. First, interactions between RAD51 and the BRC3 or BRC4 regions of BRCA2 block nucleoprotein filament formation by RAD51. Alterations to the BRC3 region that mimic cancer-associated BRCA2 mutations fail to exhibit this effect. Second, transport of RAD51 to the nucleus is defective in cells carrying a cancer-associated BRCA2 truncation. Thus, BRCA2 regulates both the intracellular localization and DNA binding ability of RAD51. Loss of these controls following BRCA2 inactivation may be a key event leading to genomic instability and tumorigenesis.