O-GlcNAc: A Sweetheart of the Cell Cycle and DNA Damage Response.
O-GlcNAc: A Sweetheart of the Cell Cycle and DNA Damage Response.
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DOI：
10.3389/fendo.2018.00415
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发表时间：
2018
影响因子：
5.2
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Liu C;Li J
在蛋白质的丝氨酸和苏氨酸残基上添加和去除O-连接的N-乙酰葡糖胺（O-GlcNAc）是一种新兴的翻译后修饰。与需要大量激酶和磷酸酶的磷酸化不同，O-GlcNAc由哺乳动物中唯一的酶O-GlcNAc转移酶（OGT）催化，并由唯一的酶O-GlcNAc酶（OGA）逆转。随着新技术的出现，鉴定O-GlcNAc酰化蛋白，然后精确定位修饰的残基并了解修饰的潜在分子功能已成为O-GlcNAc生物学的核心。O-GlcNAc在未受干扰的细胞周期中发挥多方面的作用，包括调节DNA复制、有丝分裂和胞质分裂。当细胞周期受到DNA损伤应激的挑战时，O-GlcNAc还通过修饰一系列组蛋白、激酶以及支架蛋白来保护基因组完整性。在这里，我们将重点关注细胞周期进程和DNA损伤反应，总结我们所了解的O-GlcNAc在这些过程中的作用，并设想一个更甜蜜的研究未来。
The addition and removal of O-linked N-acetylglucosamine (O-GlcNAc) to and from the Ser and Thr residues of proteins is an emerging post-translational modification. Unlike phosphorylation, which requires a legion of kinases and phosphatases, O-GlcNAc is catalyzed by the sole enzyme in mammals, O-GlcNAc transferase (OGT), and reversed by the sole enzyme, O-GlcNAcase (OGA). With the advent of new technologies, identification of O-GlcNAcylated proteins, followed by pinpointing the modified residues and understanding the underlying molecular function of the modification has become the very heart of the O-GlcNAc biology. O-GlcNAc plays a multifaceted role during the unperturbed cell cycle, including regulating DNA replication, mitosis, and cytokinesis. When the cell cycle is challenged by DNA damage stresses, O-GlcNAc also protects genome integrity via modifying an array of histones, kinases as well as scaffold proteins. Here we will focus on both cell cycle progression and the DNA damage response, summarize what we have learned about the role of O-GlcNAc in these processes and envision a sweeter research future.