分枝杆菌非典型错配修复及其在抗生素耐药中的研究进展

doi:10.16288/j.yczz.23-236

遗传 ›› 2023, Vol. 45 ›› Issue (11): 1018-1027.doi: 10.16288/j.yczz.23-236

分枝杆菌非典型错配修复及其在抗生素耐药中的研究进展

向莎莎(), 谢建平()

西南大学生命科学学院现代生物医药研究所，重庆 400715

收稿日期:2023-09-11 修回日期:2023-10-29 出版日期:2023-11-20 发布日期:2023-11-03
通讯作者: 谢建平 E-mail:1977015429@qq.com;georgex@swu.edu.cn
作者简介:向莎莎，硕士研究生，专业方向：分枝杆菌遗传学调控和分子机制。E-mail: 1977015429@qq.com。
基金资助:
国家自然科学基金项目(82072246)

Progress on the non-canonical mismatch repair in Mycobacterium and its role in antibiotic resistance

Shasha Xiang(), Jianping Xie()

Institute of Modern Biopharmaceuticals, School of Life Sciences, Southwest University, Chongqing 400715, China

Received:2023-09-11 Revised:2023-10-29 Published:2023-11-20 Online:2023-11-03
Contact: Jianping Xie E-mail:1977015429@qq.com;georgex@swu.edu.cn
Supported by:
National Natural Science Foundation of China(82072246)

摘要/Abstract

摘要：

错配修复(mismatch repair, MMR)是生物体DNA复制后的一种常见修复系统，对于维持基因组稳定性至关重要，其关键步骤由MutS和MutL蛋白家族的成员执行，尽管这种修复途径十分重要，但在许多古菌和放线菌基因组中并不存在MutS或MutL的同源蛋白。这类细菌(例如分枝杆菌等)采用另一种非典型的MMR途径，由核酸内切酶EndoMS/NucS发挥关键作用，与典型MMR蛋白(MutS/MutL)相比没有结构同源性。EndoMS/NucS介导的非典型错配修复在分枝杆菌DNA修复、突变和同源重组以及抗生素耐药等方面发挥重要作用。本文通过对比典型MMR途径和非典型MMR途径，深入阐述了分枝杆菌EndoMS/NucS介导的非典型MMR途径及其最新进展，以期为分枝杆菌错配修复分子机制带来新见解以及对分枝杆菌抗生素治疗提供研究线索。

关键词: 分枝杆菌, 错配修复, EndoMS/NucS

Abstract:

Mismatch repair (MMR) is a common repair system after DNA replication, which is critical for maintaining genomic stability. Members of the MutS and MutL protein families are involved in key steps of mismatch repair. Despite the major importance of this repair pathway, MutS-MutL are absent in almost all Actinobacteria and many Archaea. Mycobacteria and others have another non-canonical MMR pathway, in which EndoMS/NucS plays a key role and has no structural homology compared to canonical MMR proteins (MutS/MutL). EndoMS/NucS mediated non-canonical mismatch repair plays an important role in DNA repair, mutation, homologous recombination and antibiotic resistance of Mycobacterium. By comparing the classical and non-canonical MMR pathways, this paper reviews the EndoMS/NucS-mediated non-canonical MMR pathway in Mycobacterium and its recent progress. We hope to bring new insights into the molecular mechanism of mycobacterial mismatch repair as well as to provide new research clues for mycobacterial antibiotic therapy.

Key words: Mycobacterium, mismatch repair, EndoMS/NucS

向莎莎, 谢建平. 分枝杆菌非典型错配修复及其在抗生素耐药中的研究进展[J]. 遗传, 2023, 45(11): 1018-1027.

Shasha Xiang, Jianping Xie. Progress on the non-canonical mismatch repair in Mycobacterium and its role in antibiotic resistance[J]. Hereditas(Beijing), 2023, 45(11): 1018-1027.

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修复类型	生物种类	关键成分	功能
细菌典型错配修复	大肠杆菌E. coli	MutS	识别错配DNA
		MutL	下游介质
		MutH	内切酶
		UvrD	解旋酶
		Exo1/ExoX	3′→5′核酸外切酶
		ExoVII/RecJ	5′→3′核酸外切酶
		DNA聚合酶III	聚合酶
		甲基化酶Dam酶	DNA甲基化酶
		SSB结合蛋白	稳定DNA的单链区域，增强DNA聚合酶的活性
		DNA连接酶	连接酶
真核生物典型错配修复	真核生物	MutSα/MutSβ	识别错配DNA
		MutLα	下游介质；核酸内切酶
		Exo1	外切酶
		DNA聚合酶δ	聚合酶
		PCNA/RFC	激活MutLα活性
		DNA连接酶	连接酶
非典型错配修复	分枝杆菌	NucS	识别错配碱基，核酸内切酶
非典型错配修复	分枝杆菌	DnaE1聚合酶	DNA聚合酶

分枝杆菌非典型错配修复及其在抗生素耐药中的研究进展

Progress on the non-canonical mismatch repair in Mycobacterium and its role in antibiotic resistance

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