Pervasive Transcription-coupled DNA repair in E. coli.

Pervasive Transcription-coupled DNA repair in E. coli.
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E.杆菌

DOI:
10.1038/s41467-022-28871-y
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发表时间:
2022-03-30
影响因子:
16.6
通讯作者:
Nudler E
Nudler E
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Martinez B;Bharati BK;Epshtein V;Nudler E

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整体基因组修复(GGR)和转录偶联修复(TCR)已分别被视为核苷酸切除修复(NER)过程的主要和次要子途径,所述核苷酸切除修复(NER)过程从基因组中去除大体积病变。在这里,我们应用了下一代测序分析,CPD-seq,在E。大肠杆菌中,以测量水平的环丁烷嘧啶二聚体(CPD)病变之前,期间和之后,紫外线诱导的遗传毒性的压力,并因此,以确定基因组恢复率NER在一个单一的核苷酸分辨率。我们发现,主动转录是必要的,不仅修复模板链(TS),而且非模板链(NTS),和大部分的TCR是独立的Mfd -一种DNA移位酶,被认为是必要的和足够的TCR在细菌中。我们进一步表明,TS和NTS的修复增强了增加通读过去的Rho依赖性终止子。我们证明,紫外线诱导的遗传毒性应力促进全球antitermination,使TCR更容易获得的反义,基因间,和其他低转录区域。总的来说,我们的数据表明GGR和TCR基本上是细菌基因组完全修复所需的相同过程。转录偶联DNA修复已被经典地定义为模板链(TS)相对于非模板链(NTS)的优先修复。在这里,作者通过使用全基因组修复测定,CPD-seq以及RNA-seq来挑战这种经典的TCR模型,以表明TCR发生在整个E。大肠杆菌基因组-包括NTS和基因间区域。
Global Genomic Repair (GGR) and Transcription-Coupled Repair (TCR) have been viewed, respectively, as major and minor sub-pathways of the nucleotide excision repair (NER) process that removes bulky lesions from the genome. Here we applied a next generation sequencing assay, CPD-seq, in E. coli to measure the levels of cyclobutane pyrimidine dimer (CPD) lesions before, during, and after UV-induced genotoxic stress, and, therefore, to determine the rate of genomic recovery by NER at a single nucleotide resolution. We find that active transcription is necessary for the repair of not only the template strand (TS), but also the non-template strand (NTS), and that the bulk of TCR is independent of Mfd – a DNA translocase that is thought to be necessary and sufficient for TCR in bacteria. We further show that repair of both TS and NTS is enhanced by increased readthrough past Rho-dependent terminators. We demonstrate that UV-induced genotoxic stress promotes global antitermination so that TCR is more accessible to the antisense, intergenic, and other low transcribed regions. Overall, our data suggest that GGR and TCR are essentially the same process required for complete repair of the bacterial genome. Transcription-Coupled DNA repair has been classically defined as the preferential repair of the template strand (TS) over the non-template strand (NTS). Here the authors challenge this classic model of TCR by using a genome-wide repair assay, CPD-seq, as well as RNA-seq, to show that TCR occurs across the entire E. coli genome – including NTS and intergenic regions.
DOI: 10.1093/bioinformatics/btu638
发表时间: 2015-01-15
期刊: Bioinformatics (Oxford, England)
影响因子: --
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Anders S;Pyl PT;Huber W
通讯作者: Huber W
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发表时间: 2012-03-04
期刊: NATURE METHODS
影响因子: 48
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影响因子: 14.9
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发表时间: 2022-04
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影响因子: 64.8
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发表时间: 2010-08-31
影响因子: 11.1
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