Stabilization of RAD51 nucleoprotein filaments by the C-terminal region of BRCA2
Stabilization of RAD51 nucleoprotein filaments by the C-terminal region of BRCA2
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DOI：
10.1038/nsmb1245
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发表时间：
2007-06-01
影响因子：
16.8
通讯作者：
West, Stephen C.
中科院分区：
文献类型：
--
作者：
Esashi, Fumiko;Galkin, Vitold E.;West, Stephen C.
人类乳腺癌易感基因 BRCA2 是 RAD51 介导的同源重组修复调节所必需的。 BRCA2 主要通过保守的 BRC 基序与 RAD51 单体以及核蛋白丝相互作用。 BRCA2 不相关的 C 端区域也与 RAD51 相互作用。在这里，我们表明，BRCA2 C 末端通过结合两个相邻 RAD51 原聚体创建的界面，直接与 RAD51 丝而不是单体相互作用。这些相互作用使细丝稳定，使其不会因与 BRC 重复序列结合而解离。 BRCA2 C 末端与 RAD51 细丝的相互作用会导致柔性 RAD51 N 端结构域发生大幅移动，这对于调节细丝动力学非常重要。我们认为 BRCA2 C 末端区域与 RAD51 的相互作用可能促进 RAD51 多聚体在 DNA 上有效成核，从而刺激重组介导的修复。
The human breast cancer susceptibility gene BRCA2 is required for the regulation of RAD51-mediated homologous recombinational repair. BRCA2 interacts with RAD51 monomers, as well as nucleoprotein filaments, primarily though the conserved BRC motifs. The unrelated C-terminal region of BRCA2 also interacts with RAD51. Here we show that the BRCA2 C terminus interacts directly with RAD51 filaments, but not monomers, by binding an interface created by two adjacent RAD51 protomers. These interactions stabilize filaments so that they cannot be dissociated by association with BRC repeats. Interaction of the BRCA2 C terminus with the RAD51 filament causes a large movement of the flexible RAD51 N-terminal domain that is important in regulating filament dynamics. We suggest that interactions of the BRCA2 C-terminal region with RAD51 may facilitate efficient nucleation of RAD51 multimers on DNA and thereby stimulate recombination-mediated repair.