OGT 介导的组蛋白 H2B S112 GlcNAc 化调节 DNA 损伤反应。
OGT mediated histone H2B S112 GlcNAcylation regulates DNA damage response.
机构信息
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.
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.
出版信息
J Genet Genomics. 2015 Sep 20;42(9):467-75. doi: 10.1016/j.jgg.2015.07.002. Epub 2015 Jul 23.
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).
O-糖基化是一种重要的翻译后修饰，参与了许多基本的细胞过程。最近的研究表明，O-连接 N-乙酰葡萄糖胺转移酶（OGT）介导的组蛋白 H2B 丝氨酸 112 （H2B S112 O-GlcNAcylation）的 O-GlcNAcylation 在基因转录中发挥重要作用。然而，这种组蛋白修饰在 DNA 损伤反应中的作用尚未得到研究。在这项研究中，我们发现 OGT 和 OGT 介导的 H2B S112 O-GlcNAcylation 参与 DNA 损伤反应以维持基因组稳定性，并需要抵抗许多 DNA 损伤和复制应激诱导剂。OGT 介导的 H2B S112 O-GlcNAcylation 在双链断裂（DSBs）的诱导下局部增加，OGT 的耗竭或 H2B S112A 突变体的过表达损害同源重组（HR）和非同源末端连接（NHEJ）。从机制上讲，H2B S112 O-GlcNAcylation 可以结合纽姆根断裂综合征 1 （NBS1）并调节 NBS1 焦点形成。总之，我们的研究结果表明，组蛋白 O-GlcNAcylation 在 DNA 损伤反应（DDR）中具有新的功能。
Zotero 插件