RAP80将乳腺癌1号基因（BRCA1）靶向到DNA损伤位点的特定泛素结构上。
RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites.
作者信息
Sobhian Bijan, Shao Genze, Lilli Dana R, Culhane Aedín C, Moreau Lisa A, Xia Bing, Livingston David M, Greenberg Roger A
机构信息
Dana-Farber Cancer Institute and Department of Genetics and Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
出版信息
Science. 2007 May 25;316(5828):1198-202. doi: 10.1126/science.1139516.
Abstract
Mutations affecting the BRCT domains of the breast cancer-associated tumor suppressor BRCA1 disrupt the recruitment of this protein to DNA double-strand breaks (DSBs). The molecular structures at DSBs recognized by BRCA1 are presently unknown. We report the interaction of the BRCA1 BRCT domain with RAP80, a ubiquitin-binding protein. RAP80 targets a complex containing the BRCA1-BARD1 (BRCA1-associated ring domain protein 1) E3 ligase and the deubiquitinating enzyme (DUB) BRCC36 to MDC1-gammaH2AX-dependent lysine(6)- and lysine(63)-linked ubiquitin polymers at DSBs. These events are required for cell cycle checkpoint and repair responses to ionizing radiation, implicating ubiquitin chain recognition and turnover in the BRCA1-mediated repair of DSBs.
摘要
影响乳腺癌相关肿瘤抑制因子BRCA1的BRCT结构域的突变会破坏该蛋白与DNA双链断裂（DSB）的结合。目前尚不清楚BRCA1识别的DSB处的分子结构。我们报道了BRCA1的BRCT结构域与RAP80（一种泛素结合蛋白）的相互作用。RAP80将一个包含BRCA1 - BARD1（BRCA1相关环结构域蛋白1）E3连接酶和去泛素化酶（DUB）BRCC36的复合物靶向到DSB处依赖MDC1 - γH2AX的赖氨酸（6）-和赖氨酸（63）-连接的泛素聚合物上。这些事件是细胞周期检查点以及对电离辐射的修复反应所必需的，这表明泛素链识别和周转参与了BRCA1介导的DSB修复。
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