Prakash Rohit, Zhang Yu, Feng Weiran, Jasin Maria
Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065.
Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065 Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, New York 10065.
Cold Spring Harb Perspect Biol. 2015 Apr 1;7(4):a016600. doi: 10.1101/cshperspect.a016600.
Homologous recombination (HR) is a major pathway for the repair of DNA double-strand breaks in mammalian cells, the defining step of which is homologous strand exchange directed by the RAD51 protein. The physiological importance of HR is underscored by the observation of genomic instability in HR-deficient cells and, importantly, the association of cancer predisposition and developmental defects with mutations in HR genes. The tumor suppressors BRCA1 and BRCA2, key players at different stages of HR, are frequently mutated in familial breast and ovarian cancers. Other HR proteins, including PALB2 and RAD51 paralogs, have also been identified as tumor suppressors. This review summarizes recent findings on BRCA1, BRCA2, and associated proteins involved in human disease with an emphasis on their molecular roles and interactions.
同源重组（HR）是哺乳动物细胞中DNA双链断裂修复的主要途径，其决定性步骤是由RAD51蛋白介导的同源链交换。HR缺陷细胞中基因组不稳定的现象，以及重要的是，HR基因突变与癌症易感性和发育缺陷的关联，都突显了HR在生理上的重要性。肿瘤抑制因子BRCA1和BRCA2是HR不同阶段的关键参与者，在家族性乳腺癌和卵巢癌中经常发生突变。其他HR蛋白，包括PALB2和RAD51旁系同源物，也已被鉴定为肿瘤抑制因子。本综述总结了关于BRCA1、BRCA2以及参与人类疾病的相关蛋白的最新研究发现，重点关注它们的分子作用和相互作用。
