Wu Chen, Li Jiaheng, Lu Lingzi, Li Mengyuan, Yuan Yanqiu, Li Jing
College of Life Sciences, Institute of Life Sciences and Green Development, Hebei University, Baoding, Hebei, China.
College of Life Sciences, Institute of Life Sciences and Green Development, Hebei University, Baoding, Hebei, China.
J Biol Chem. 2024 Apr;300(4):107141. doi: 10.1016/j.jbc.2024.107141. Epub 2024 Mar 4.
The past 4 decades have witnessed tremendous efforts in deciphering the role of O-GlcNAcylation in a plethora of biological processes. Chemists and biologists have joined hand in hand in the sweet adventure to unravel this unique and universal yet uncharted post-translational modification, and the recent advent of cutting-edge chemical biology and mass spectrometry tools has greatly facilitated the process. Compared with O-GlcNAc, DNA damage response (DDR) is a relatively intensively studied area that could be traced to before the elucidation of the structure of DNA. Unexpectedly, yet somewhat expectedly, O-GlcNAc has been found to regulate various DDR pathways: homologous recombination, nonhomologous end joining, base excision repair, and translesion DNA synthesis. In this review, we first cover the recent structural studies of the O-GlcNAc transferase and O-GlcNAcase, the elegant duo that "writes" and "erases" O-GlcNAc modification. Then we delineate the intricate roles of O-GlcNAc transferase and O-GlcNAcase in DDR. We envision that this is only the beginning of our full appreciation of how O-GlcNAc regulates the blueprint of life-DNA.
在过去的40年里，人们在解读O-连接的N-乙酰葡糖胺化（O-GlcNAcylation）在众多生物学过程中的作用方面付出了巨大努力。化学家和生物学家携手踏上这场甜蜜的探索之旅，以揭开这种独特、普遍却未知的翻译后修饰，而前沿化学生物学和质谱工具的出现极大地推动了这一进程。与O-GlcNAc相比，DNA损伤反应（DDR）是一个研究相对深入的领域，其研究甚至可以追溯到DNA结构被阐明之前。出人意料却又在情理之中的是，人们发现O-GlcNAc能够调控多种DDR途径：同源重组、非同源末端连接、碱基切除修复和跨损伤DNA合成。在这篇综述中，我们首先介绍O-GlcNAc转移酶和O-GlcNAcase的最新结构研究，这对精妙组合负责“书写”和“擦除”O-GlcNAc修饰。接着，我们阐述O-GlcNAc转移酶和O-GlcNAcase在DDR中的复杂作用。我们预计，这仅仅是我们全面认识O-GlcNAc如何调控生命蓝图——DNA的开端。
