Esashi Fumiko, Galkin Vitold E, Yu Xiong, Egelman Edward H, West Stephen C
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK.
Nat Struct Mol Biol. 2007 Jun;14(6):468-74. doi: 10.1038/nsmb1245. Epub 2007 May 21.
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.
人类乳腺癌易感基因BRCA2是RAD51介导的同源重组修复调控所必需的。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末端区域也与RAD51相互作用。在这里，我们表明BRCA2 C末端通过结合由两个相邻RAD51原体形成的界面，直接与RAD51丝相互作用，而不与单体相互作用。这些相互作用稳定了丝，使其不会因与BRC重复序列结合而解离。BRCA2 C末端与RAD51丝的相互作用导致灵活的RAD51 N末端结构域发生大的移动，这对调节丝的动力学很重要。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上的有效成核，从而刺激重组介导的修复。
