分枝杆菌非同源末端连接生理功能及其在基因编辑中的应用

Non-homologous end-joining (NHEJ): physiological function in Mycobacterium and application in gene editing

摘要:

DNA双链断裂(double-strand breaks,DSBs)被认为是生物体内最为严重的一种DNA损伤形式，它不仅会导致基因组失去稳定性，还可能引发细胞死亡。同源重组(homologous recombination,HR)和非同源末端连接(non-homologous end joining,NHEJ)是2种主要的DNA双链断裂修复方法。参与NHEJ途径的核心成分在酵母和人中高度保守，部分细菌如分枝杆菌、铜绿假单胞菌和枯草芽孢杆菌，也具有NHEJ修复能力。NHEJ可能在分枝杆菌潜伏期的双链修复中发挥重要作用。本文对分枝杆菌中NHEJ的修复机制及其关键组分进行了系统综述，并探讨了其在基因编辑领域的应用前景，深入阐述了分枝杆菌NHEJ途径及其最新研究进展，为分枝杆菌NHEJ修复分子机制提供了新见解并为分枝杆菌NHEJ的应用提供了理论基础。

Abstract:

DNA double-strand breaks represent a common type of serious DNA damage in living organisms, causing instability of the genome and leading to cell death. Homologous recombination and non-homologous end-joining (NHEJ) are the two main ways to repair DNA double-strand breaks. The core components involved in the NHEJ pathway are highly conserved in both yeast and humans. A few bacteria such as Mycobacterium, Pseudomonas aeruginosa, and Bacillus subtilis also have the NHEJ mechanism. NHEJ plays a key role in the double strand repair of Mycobacterium in latency. This paper summarizes the mechanism and important components of NHEJ in Mycobacterium, introduces the application of NHEJ in gene editing, and reviews the research progress of the NHEJ pathway in Mycobacterium. We hope to bring new insights into the molecular mechanism and provide clues for the application of NHEJ in Mycobacterium.