The Deubiquitylating Enzyme USP4 Cooperates with CtIP in DNA Double-Strand Break End Resection
Hailong Liua, Haoxing Zhanga, Xiaohui Wanga, Qingsong Tianb, Zhaohua Hub, Changmin Pengc d, Pei Jianga, Tingting Wange f, Wei Guoe f, Yali Chena, Xinzhi Lib, Pumin Zhanga g✉, Huadong Peia h✉
- aState Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China
- bDepartment of Orthopedics, Renhe Hospital of Three Gorges University, Yichang 443001, China
- cKey Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Industrial Microbiology Key Lab, College of Biotechnology, Tianjin University of Science and Technology, No. 29, 13ST. TEDA, Tianjin 300457, China
- dKey Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Industrial Microbiology Key Lab, College of Biotechnology, Tianjin University of Science and Technology, No. 29, 13ST. TEDA, Tianjin, 300457, China
- eDepartment of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
- fDepartment of General Surgery, Beijing Friendship Hospital,Capital Medical University, Beijing 100050, China
- gState Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China. Electronic address: pzhang@bcm.edu
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Abstract
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.
TL;DRIt is found that the deubiquitylating enzyme USP4 directly participates in DSB resection and homologous recombination (HR) and is identified as a key regulator of DNA DSB end resection. (Semantic Scholar)