Distinct functions of BRCA1 and BRCA2 in double-strand break repair

Individuals carrying BRCA mutations are predisposed to breast cancer. The BRCA1 and BRCA2 proteins are required for homologous recombination and DNA break repair, leading to the suggestion that they act in concert. However, direct evidence of a stable BRCA1/BRCA2 complex has not been demonstrated. Rather, the two proteins have been found as constituents of discrete, but perhaps nonexclusive complexes that are critical for repair. We discuss the interaction of BRCA1 with the BACH1 and BARD1 proteins, and suggest that the pleiotropic nature of mutations in BRCA1 may be associated with defects in protein–protein interactions. In contrast, the role of BRCA2 in DNA repair may be more defined by its direct interaction with the RAD51 recombinase.携带BRCA突变的个体易罹患乳腺癌。BRCA1与BRCA2蛋白是同源重组（Homologous Recombination）及DNA断裂修复（DNA Break Repair）过程所必需的，因此学界曾推测二者协同发挥作用。然而，稳定存在的BRCA1/BRCA2复合物（BRCA1/BRCA2 Complex）的直接证据尚未得到证实。与之相反，研究发现这两种蛋白均为若干离散但可能并非排他的修复关键复合物的组成成分。本文探讨了BRCA1与BACH1、BARD1蛋白的相互作用，并提出BRCA1突变的多效性特征可能与其蛋白质相互作用（Protein-Protein Interaction）缺陷相关。与之相对，BRCA2在DNA修复中的作用或可通过其与RAD51重组酶（RAD51 Recombinase）的直接相互作用得到更明确的阐释。