title: OGT mediated histone H2B S112 GlcNAcylation regulates DNA damage response.
abstract: O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S112 GlcNAcylation) plays an important role in gene transcription. However, the role of this histone modification in DNA damage response has not been studied yet. In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress-inducing agents. OGT mediated H2B S112 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). Mechanistically, H2B S112 GlcNAcylation could bind Nijmegen breakage syndrome 1 (NBS1) and regulate NBS1 foci formation. Taken together, our results demonstrate a new function of histone O-GlcNAcylation in DNA damage response (DDR).
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, Tianjin 300457, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China; School of Nursing and Medical Technology, Jianghan University, Wuhan 430056, China.
authors.forename: Panfei
authors.initials: P
authors.lastname: Wang
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, Tianjin 300457, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China; School of Nursing and Medical Technology, Jianghan University, Wuhan 430056, China.
authors.forename: Changmin
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Radiotherapy, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin 301800, China; School of Nursing and Medical Technology, Jianghan University, Wuhan 430056, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
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: Yali
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Nursing and Medical Technology, Jianghan University, Wuhan 430056, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Radiotherapy, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin 301800, China. Electronic address: tjhanbaolin@163.com.
authors.forename: Baolin
authors.initials: B
authors.lastname: Han
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, Tianjin 300457, China; 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: D000117:Acetylglucosamine / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D059766:DNA End-Joining Repair; D004261:DNA Replication; D006031:Glycosylation; D045325:HCT116 Cells; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D059765:Homologous Recombination; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*
chemical_list: D006657:Histones; D012694:Serine; D017351:N-Acetylglucosaminyltransferases; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase; D000117:Acetylglucosamine
keywords: DNA damage response; H2B S112 GlcNAcylation; NBS1; OGT