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Updated: Jun 17, 2025

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一个额外的校对员有助于DNA复制真实性在mycobacteria

Ming-Zhi Deng¹, Qingyun Liu², Shu-Jun Cui^1,3

¹Key Laboratory of Medical Molecular Virology of the Ministry of Education/Ministry of Health, Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.

Proceedings of the National Academy of Sciences of the United States of America

|August 14, 2024

概括

非正规的DnaQ作为mycobacteria中的第二个校对者,与PHP域合作,以确保DNA复制的真实性. 它的损失导致突变和复制压力的增加,可能有助于Mycobacterium结核病的适应.

科学领域:

微生物学微生物学
分子生物学分子生物学
遗传学是一个遗传学.

背景情况:

基因复制的真实性对于基因组稳定性至关重要,由校对机制维护.
虽然大肠杆菌使用e-外核酶DnaQ,但许多细菌使用聚合酶和histidinol酸酶 (PHP) 域进行校对.
在细菌校对中,不同,非正规的DnaQ同类的作用仍然在很大程度上未被描述.

研究的目的:

为了研究非正典DnaQ作为mycobacteria中的校对员的功能.
阐明DNA复制过程中DnaQ与PHP域的相互作用和协同作用.
探索DnaQ功能的影响和Mycobacterium结核病 (Mtb) 适应和耐药性的变化.

主要方法:

突变积累测定与Mycolicibacterium smegmatis的全基因组测序相结合.
对DnaQ与β结合的分析及其与PHP域的相互作用.
在Mycobacterium结核病的临床分离物中对dnaQ的序列多态性分析.

主要成果:

在M.中DnaQ的耗尽. smegmatis显著增加了突变率,表现出AT偏差的突变发生和同聚合物通道中的高插入/删除.
证明Mycobacterial DnaQ能够与β结合,并与PHP域校对器协同工作.
DnaQ功能的丧失导致了复制叉功能障碍,增长减弱,并在诺基诺应激下增加了突变发生.
在4.3血统中流行的一种MtbDnaQ变异与超变性和耐药性有关.

结论:

非正典DnaQ功能作为一个额外的,必要的校对在菌根菌,补充PHP域的活动.
提出了一个配对校对模型,在DnaQ和PHP域之间进行分工.
在Mtb中的DnaQ变异可以驱动超变性并导致耐药性,这表明一种由突变驱动的进化适应途径.

关键词:

DNA复制的真实性 DNA复制的真实性 DnaQQ 在线观看这是Mycobacterium.药物耐药性耐药性药物耐药性校对阅读校对阅读

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