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转录修复偶联因子Mfd以依赖于上下文的方式预防和促进诱变。

The Transcription-Repair Coupling Factor Mfd Prevents and Promotes Mutagenesis in a Context-Dependent Manner.

作者信息

Lindsey-Boltz Laura A, Sancar Aziz

机构信息

Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC, United States.

出版信息

Front Mol Biosci. 2021 May 20;8:668290. doi: 10.3389/fmolb.2021.668290. eCollection 2021.

DOI:10.3389/fmolb.2021.668290
PMID:34095223
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8174841/
Abstract

The (mutation frequency decline) gene was identified by screening an auxotrophic strain exposed to UV and held in a minimal medium before plating onto rich or minimal agar plates. It was found that, under these conditions, holding cells in minimal (nongrowth) conditions resulted in mutations that enabled cells to grow on minimal media. Using this observation as a starting point, a mutant was isolated that failed to mutate to auxotrophy under the prescribed conditions, and the gene responsible for this phenomenon (mutation frequency decline) was named . Later work revealed that encoded a translocase that recognizes a stalled RNA polymerase (RNAP) at damage sites and binds to the stalled RNAP, recruits the nucleotide excision repair damage recognition complex UvrAUvrB to the site, and facilitates damage recognition and repair while dissociating the stalled RNAP from the DNA along with the truncated RNA. Recent single-molecule and genome-wide repair studies have revealed time-resolved features and structural aspects of this transcription-coupled repair (TCR) phenomenon. Interestingly, recent work has shown that in certain bacterial species, also plays roles in recombination, bacterial virulence, and the development of drug resistance.

摘要

(突变频率下降)基因是通过筛选一株营养缺陷型菌株来鉴定的,该菌株先暴露于紫外线,然后在接种到丰富或基本琼脂平板之前保存在基本培养基中。结果发现,在这些条件下,将细胞保存在基本(非生长)条件下会导致突变,使细胞能够在基本培养基上生长。以这一观察结果为起点,分离出一个在规定条件下不会突变为营养缺陷型的突变体,负责这种现象(突变频率下降)的基因被命名为 。后来的研究表明, 编码一种转位酶,该酶在损伤位点识别停滞的RNA聚合酶(RNAP)并与之结合,将核苷酸切除修复损伤识别复合物UvrAUvrB募集到该位点,促进损伤识别和修复,同时将停滞的RNAP与DNA以及截短的RNA一起从DNA上解离。最近的单分子和全基因组修复研究揭示了这种转录偶联修复(TCR)现象的时间分辨特征和结构方面。有趣的是,最近的研究表明,在某些细菌物种中, 还在重组、细菌毒力和耐药性发展中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97c/8174841/c7ce8ae339c2/fmolb-08-668290-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97c/8174841/76262f37a584/fmolb-08-668290-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97c/8174841/c7ce8ae339c2/fmolb-08-668290-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97c/8174841/76262f37a584/fmolb-08-668290-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b97c/8174841/c7ce8ae339c2/fmolb-08-668290-g002.jpg

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Structural basis for transcription complex disruption by the Mfd translocase.Mfd 易位酶破坏转录复合物的结构基础。
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Mfd regulates RNA polymerase association with hard-to-transcribe regions in vivo, especially those with structured RNAs.Mfd 调节 RNA 聚合酶与体内难转录区域的结合,特别是那些具有结构 RNA 的区域。
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Nucleic Acids Res. 2022 Apr 8;50(6):3018-3041. doi: 10.1093/nar/gkac174.
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