Role of BRCA2 in control of the RAD51 recombination and DNA repair protein

Individuals carrying BRCA2 mutations are predisposed to breast and ovarian cancers. Here, we show that BRCA2 plays a dual role in regulating the actio ns of RAD51, a protein essential for homologous recombination and DNA repai r. First, interactions between RAD51 and the BRC3 or BRC4 regions of BRCA2 block nucleoprotein filament formation by RAD51. Alterations to the BRC3 re gion that mimic cancer-associated BRCA2 mutations fail to exhibit this effe ct. Second, transport of RAD51 to the nucleus is defective in cells carryin g a cancer-associated BRCA2 truncation. Thus, BRCA2 regulates both the intr acellular localization and DNA binding ability of RAD51. Loss of these cont rols following BRCA2 inactivation may be a key event leading to genomic ins tability and tumorigenesis.