去泛素化酶USP4与CtIP在DNA双链断裂末端切除过程中协同作用。
The Deubiquitylating Enzyme USP4 Cooperates with CtIP in DNA Double-Strand Break End Resection.
作者信息
Liu Hailong, Zhang Haoxing, Wang Xiaohui, Tian Qingsong, Hu Zhaohua, Peng Changmin, Jiang Pei, Wang TingTing, Guo Wei, Chen Yali, Li Xinzhi, Zhang Pumin, Pei Huadong
机构信息
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Department of Orthopedics, Renhe Hospital of Three Gorges University, Yichang 443001, China.
出版信息
Cell Rep. 2015 Oct 6;13(1):93-107. doi: 10.1016/j.celrep.2015.08.056. Epub 2015 Sep 17.
DNA end resection is a highly regulated and critical step in DNA double-stranded break (DSB) repair. In higher eukaryotes, DSB resection is initiated by the collaborative action of CtIP and the MRE11-RAD50-NBS1 (MRN) complex. Here, we find that the deubiquitylating enzyme USP4 directly participates in DSB resection and homologous recombination (HR). USP4 confers resistance to DNA damage-inducing agents. Mechanistically, USP4 interacts with CtIP and MRN via a specific, conserved region and the catalytic domain of USP4, respectively, and regulates CtIP recruitment to sites of DNA damage. We also find that USP4 autodeubiquitylation is essential for its HR functions. Collectively, our findings identify USP4 as a key regulator of DNA DSB end resection.
DNA 末端切除是 DNA 双链断裂（DSB）修复过程中一个受到高度调控的关键步骤。在高等真核生物中，DSB 切除由 CtIP 与 MRE11-RAD50-NBS1（MRN）复合物的协同作用启动。在此，我们发现去泛素化酶 USP4 直接参与 DSB 切除和同源重组（HR）。USP4 赋予细胞对 DNA 损伤诱导剂的抗性。从机制上讲，USP4 分别通过一个特定的保守区域和 USP4 的催化结构域与 CtIP 和 MRN 相互作用，并调节 CtIP 募集到 DNA 损伤位点。我们还发现 USP4 自身去泛素化对其 HR 功能至关重要。总之，我们的研究结果确定 USP4 是 DNA DSB 末端切除的关键调节因子。
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