遗传 ›› 2019, Vol. 41 ›› Issue (1): 29-40.doi: 10.16288/j.yczz.18-112

• 综述 • 上一篇    下一篇

组蛋白泛素化修饰及其在DNA损伤应答中的作用

张卿义1,张樱子2,沈凯1,张舒羽2,曹建平2   

  1. 1. 苏州大学医学部第一临床医学院,苏州 215123
    2. 苏州大学医学部放射医学与防护学院,苏州 215123
  • 收稿日期:2018-07-10 修回日期:2018-09-04 出版日期:2019-01-20 发布日期:2018-10-19
  • 作者简介:张卿义,本科在读,专业方向:临床医学。E-mail: zhangqingyi@outlook.com
  • 基金资助:
    国家级大学生创新创业训练计划(编号:201610285039Z,201610285045Z)资助

Histone ubiquitylation and its roles in DNA damage response

Zhang Qingyi1,Zhang Yingzi2,Shen Kai1,Zhang Shuyu2,Cao Jianping2   

  1. 1. The First Clinical Medical School, Soochow University, Suzhou 215123, China
    2. School of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Science, Soochow University, Suzhou 215123, China
  • Received:2018-07-10 Revised:2018-09-04 Online:2019-01-20 Published:2018-10-19
  • Supported by:
    [Supported by the National Students’ Platform for Innovation and Entrepreneurship Training Program (Nos. 201610285039Z, 201610285045Z)]

摘要:

泛素化修饰是真核生物细胞内重要的翻译后修饰类型,通过调节蛋白质活性、稳定性和亚细胞定位广泛参与细胞内各项信号传导与代谢过程,对维持正常生命活动具有重要意义。组蛋白作为染色质中主要的蛋白成分,与DNA复制转录、修复等行为密切相关,是研究翻译后修饰的热点。DNA损伤后,组蛋白泛素化修饰通过调节核小体结构、激活细胞周期检查点、影响修复因子的招募与装配等诸多途径参与损伤应答。同时,组蛋白泛素化修饰还能调节其他位点翻译后修饰,并通过这种串扰(crosstalk)作用调节DNA损伤应答。本文介绍了组蛋白泛素化修饰的主要位点和相关组分(包括E3连接酶、去泛素化酶与效应分子),以及这些修饰作用共同编译形成的信号网络在DNA损伤应答中的作用,最后总结了目前该领域研究所面临的一些问题,以期为科研人员进一步探索组蛋白密码在DNA损伤应答中的作用提供参考。

关键词: 组蛋白, 泛素化修饰, DNA损伤应答, 串扰

Abstract:

Ubiquitylation is an essential type of protein post-translational modifications (PTMs) in eukaryotes, which mediates various biological processes by regulating the subcellular localization, activity, and stability of proteins. Histones, as the main protein ingredients of chromatin, are closely coupled with DNA activities such as replication, transcription and repair, and therefore are the hotspots of PTMs. After DNA damage, histone ubiquitylations are involved in DNA damage response (DDR) by regulating nucleosome structure, activating cell cycle checkpoints, remodeling the nucleosome, and the recruitment and assembly of repair factors. Meanwhile, histone ubiquitylations can also crosstalk with other types of PTMs to regulate DDR processes. In this review, we summarize how the site-specific histone ubiquitylation forms signal network and contributes to DDR, which may shed light on the further study of how histone codes formed by histone PTMs affect the entire DDR processes.

Key words: histone, ubiquitylation, DNA damage response (DDR), crosstalk