title: The Deubiquitylating Enzyme USP4 Cooperates with CtIP in DNA Double-Strand Break End Resection.
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.
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Haoxing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Renhe Hospital of Three Gorges University, Yichang 443001, China.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Tian
authors.affiliation: Department of Orthopedics, Renhe Hospital of Three Gorges University, Yichang 443001, China.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Key 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.
authors.forename: Changmin
authors.initials: C
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: TingTing
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Renhe Hospital of Three Gorges University, Yichang 443001, China.
authors.forename: Xinzhi
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China. Electronic address: pzhang@bcm.edu.
authors.forename: Pumin
authors.initials: P
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China. Electronic address: peihuadong@hotmail.com.
authors.forename: Huadong
authors.initials: H
authors.lastname: Pei
mesh_terms: D017766:Acid Anhydride Hydrolases; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004706:Endodeoxyribonucleases; D006367:HeLa Cells; D059765:Homologous Recombination; D006801:Humans; D000076228:MRE11 Homologue Protein; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*; D064570:Ubiquitin-Specific Proteases; D054875:Ubiquitination
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; C112156:NBN protein, human; D009687:Nuclear Proteins; C486203:USP4 protein, human; D004247:DNA; D004706:Endodeoxyribonucleases; D000076228:MRE11 Homologue Protein; C410741:RBBP8 protein, human; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes