Abstract
DNA is the hereditary material in humans and almost all other organisms. It is essential for maintaining accurate transmission of genetic information. In the life cycle, DNA replication, cell division, or genome damage, including that caused by endogenous and exogenous agents, may cause DNA aberrations. Of all forms of DNA damage, DNA double-strand breaks (DSBs) are the most serious. If the repair function is defective, DNA damage may cause gene mutation, genome instability, and cell chromosome loss, which in turn can even lead to tumorigenesis. DNA damage can be repaired through multiple mechanisms. Homologous recombination (HR) and non-homologous end joining (NHEJ) are the two main repair mechanisms for DNA DSBs. Increasing amounts of evidence reveal that protein modifications play an essential role in DNA damage repair. Protein deubiquitination is a vital post-translational modification which removes ubiquitin molecules or polyubiquitinated chains from substrates in order to reverse the ubiquitination reaction. This review discusses the role of deubiquitinating enzymes (DUBs) in repairing DNA DSBs. Exploring the molecular mechanisms of DUB regulation in DSB repair will provide new insights to combat human diseases and develop novel therapeutic approaches.
摘要
DNA是人类和几乎所有有机体的遗传物质,它对于保持遗传信息的准确传递至关重要。在生命周期中,DNA复制、细胞分裂、基因组损伤,以及由内源性和外源性因素引起的损伤,都可能引起DNA损伤。在所有形式的DNA损伤中,DNA双链断裂(DSB)是最严重的。如果修复功能有缺陷,DNA损伤可能导致基因突变、基因组不稳定、细胞染色体丢失,进而导致肿瘤的发生。DNA损伤可以通过多种机制修复。同源重组(HR)和非同源末端连接(NHEJ)是DSB的两种主要修复机制。另外,大量研究表明,蛋白质修饰在DNA损伤修复中起着至关重要的作用。蛋白质的去泛素化是一种重要的翻译后修饰,它可以从底物中去除泛素分子或多泛素链,从而逆转泛素化降解,稳定底物蛋白。本文综述了去泛素化酶(DUB)在DSB损伤修复中的作用,探讨DUB调控DSB修复的分子机制,为开发人类疾病的新疗法提供了全新思路。
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Change history
08 April 2021
The typesetting format of the online version of the first issue (2021 22(01)) of Journal of Zhejiang University-SCIENCE B is different from that of the printed version (but all the text, figure and table contents in the article are correct). This is due to the new typesetting company adopted this year.
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The research was supported by the National Natural Science Foundation of China (Nos. 91749115 and 81872298) and the Natural Science Foundation of Jiangxi Province (No. 20181BAB205044), China. The authors thank all Jian YUAN laboratory members for critical comments on the manuscript.
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Yunhui LI participated in searching and summarizing the relevant literature as well as designing and writing the manuscript. Jian YUAN provided the theme and design, and edited the manuscript. Both authors have read and approved the final manuscript.
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Yun-hui LI and Jian YUAN declare that they have no conflicts of interest.
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Li, Y., Yuan, J. Role of deubiquitinating enzymes in DNA double-strand break repair. J. Zhejiang Univ. Sci. B 22, 63–72 (2021). https://doi.org/10.1631/jzus.B2000309
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DOI: https://doi.org/10.1631/jzus.B2000309
Key words
- Deubiquitinating enzymes (DUBs)
- DNA double-strand breaks (DSBs)
- DNA repair
- Non-homologous end joining (NHEJ)
- Homologous recombination (HR)