Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response
Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response
复制标题
DOI：
10.1126/science.1139621
复制
发表时间：
2007-05-25
期刊：
影响因子：
56.9
通讯作者：
Yu, Xiaochun
中科院分区：
文献类型：
--
作者：
Kim, Hongtae;Chen, Junjie;Yu, Xiaochun
乳腺癌易感基因1（BRCA 1）的突变与乳腺癌和卵巢癌的风险增加有关。BRCA 1参与细胞DNA损伤反应。我们报告了受体相关蛋白80（RAP 80）作为BRCA 1相互作用蛋白在人类中的鉴定。RAP 80含有一个串联的泛素相互作用基序结构域，该结构域是RAP 80在体外与泛素结合以及在体内形成损伤诱导灶所必需的。此外，RAP 80特异性地将BRCA 1募集到DNA损伤位点，并与BRCA 1一起在G（2）/M检查点控制中发挥作用。总之，这些结果表明存在一个泛素化依赖的信号通路参与DNA损伤反应。
Mutations in the breast cancer susceptibility gene 1 (BRCA1) are associated with an increased risk of breast and ovarian cancers. BRCA1 participates in the cellular DNA damage response. We report the identification of receptor-associated protein 80 (RAP80) as a BRCA1-interacting protein in humans. RAP80 contains a tandem ubiquitin-interacting motif domain, which is required for its binding with ubiquitin in vitro and its damage-induced foci formation in vivo. Moreover, RAP80 specifically recruits BRCA1 to DNA damage sites and functions with BRCA1 in G(2)/M checkpoint control. Together, these results suggest the existence of a ubiquitination-dependent signaling pathway involved in the DNA damage response.