title: OGT restrains the expansion of DNA damage signaling.
abstract: O-linked N-acetylglucosamine linkage (O-GlcNAcylation) to serine or threonine residues regulates numerous biological processes; however, its role in DNA damage response remains elusive. Here, we found that O-GlcNAcylation is induced by DNA damage response. O-GlcNAc transferase (OGT), the solo enzyme for O-GlcNAcylation, relocates to the sites of DNA damage and induces the O-GlcNAcylation of histone H2AX and mediator of DNA damage checkpoint 1 (MDC1). The O-GlcNAcylation negatively regulates DNA double-strand break-induced phosphorylation of H2AX and MDC1 by restraining the expansion of these phosphorylation events from the sites of DNA damage. Therefore, our study reveals the molecular mechanism and biological function of OGT-dependent O-GlcNAcylation in response to DNA damage.
authors.affiliation: Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA xyu@coh.org.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Yu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D059447:Cell Cycle Checkpoints / Q000235:genetics; D018797:Cell Cycle Proteins; D002470:Cell Survival / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D006031:Glycosylation; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D006657:Histones; C413163:MDC1 protein, human; D009687:Nuclear Proteins; D015534:Trans-Activators; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase