Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response
Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response
复制标题
DOI：
10.1126/science.1139476
复制
发表时间：
2007-05-25
期刊：
影响因子：
56.9
通讯作者：
Elledge, Stephen J.
中科院分区：
文献类型：
--
作者：
Wang, Bin;Matsuoka, Shuhei;Elledge, Stephen J.
乳腺癌和卵巢癌易感蛋白BRCA1的BRCT重复对于肿瘤抑制是必不可少的。磷肽亲和蛋白质组学分析确定了一个蛋白质Abraxas，它通过一个磷酸-Ser-X-X-Phe基序直接结合BRCA1 BRCT重复序列。Abraxas将BRCA1与BACH1(BRCA1相关的C末端解旋酶)和CtIP(CtBP相互作用蛋白)相互排斥，形成第三种类型的BRCA1复合体。Abraxas将包含泛素相互作用基序(UIM)的蛋白质RAP80招募到BRCA1。Abraxas和RAP80都是抗DNA损伤、G(2)-M检查点控制和DNA修复所必需的。RAP80是BRCA1在损伤的DNA(焦点)上最佳积累所必需的，只有UIM结构域能够形成焦点。RAP80-Abraxas复合体可能有助于将BRCA1招募到DNA损伤位置，部分是通过识别泛素化的蛋白质。
The BRCT repeats of the breast and ovarian cancer predisposition protein BRCA1 are essential for tumor suppression. Phosphopeptide affinity proteomic analysis identified a protein, Abraxas, that directly binds the BRCA1 BRCT repeats through a phospho- Ser-X-X-Phe motif. Abraxas binds BRCA1 to the mutual exclusion of BACH1 (BRCA1-associated C-terminal helicase) and CtIP (CtBP-interacting protein), forming a third type of BRCA1 complex. Abraxas recruits the ubiquitin-interacting motif (UIM)-containing protein RAP80 to BRCA1. Both Abraxas and RAP80 were required for DNA damage resistance, G(2)- M checkpoint control, and DNA repair. RAP80 was required for optimal accumulation of BRCA1 on damaged DNA ( foci) in response to ionizing radiation, and the UIM domains alone were capable of foci formation. The RAP80-Abraxas complex may help recruit BRCA1 to DNA damage sites in part through recognition of ubiquitinated proteins.