Mutations in the BRCA1 and BRCA2 genes predispose afflicted individuals to breast, ovarian, and other cancers. The BRCA-encoded products form complexes with other tumor suppressor proteins and with the recombinase enzyme RAD51 to mediate chromosome damage repair by homologous recombination and also to protect stressed DNA replication forks against spurious nucleolytic attrition. Understanding how the BRCA tumor suppressor network executes its biological functions would provide the foundation for developing targeted cancer therapeutics, but progress in this area has been greatly hampered by the challenge of obtaining purified BRCA complexes for mechanistic studies. In this article, we review how recent effort begins to overcome this technical challenge, leading to functional and structural insights into the biochemical attributes of these complexes and the multifaceted roles that they fulfill in genome maintenance. We also highlight the major mechanistic questions that remain.

中文翻译：

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通过同源重组修复染色体损伤的BRCA肿瘤抑制网络。

BRCA1和BRCA2基因的突变使患病个体更易患乳腺癌，卵巢癌和其他癌症。BRCA编码的产物与其他肿瘤抑制蛋白和重组酶RAD51形成复合物，以通过同源重组介导染色体损伤修复，还可以保护压力较大的DNA复制叉免受伪造的核酸水解损耗。了解BRCA抑癌网络如何执行其生物学功能将为开发靶向的癌症治疗方法提供基础，但是，获得纯化的BRCA复合物用于机理研究的挑战极大地阻碍了这一领域的进展。在本文中，我们将回顾最近的工作如何开始克服这一技术挑战，导致对这些复合物的生化属性及其在基因组维持中发挥的多方面作用的功能和结构见解。我们还将重点介绍仍然存在的主要机械问题。