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Pervasive Transcription-coupled DNA repair in E. coli

Author

Listed:
  • Britney Martinez

    (NYU Grossman School of Medicine)

  • Binod K. Bharati

    (NYU Grossman School of Medicine
    Howard Hughes Medical Institute, NYU Grossman School of Medicine)

  • Vitaly Epshtein

    (NYU Grossman School of Medicine)

  • Evgeny Nudler

    (NYU Grossman School of Medicine
    Howard Hughes Medical Institute, NYU Grossman School of Medicine)

Abstract

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.

Suggested Citation

  • Britney Martinez & Binod K. Bharati & Vitaly Epshtein & Evgeny Nudler, 2022. "Pervasive Transcription-coupled DNA repair in E. coli," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28871-y
    DOI: 10.1038/s41467-022-28871-y
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    References listed on IDEAS

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    1. Laure Botella & Julien Vaubourgeix & Jonathan Livny & Dirk Schnappinger, 2017. "Depleting Mycobacterium tuberculosis of the transcription termination factor Rho causes pervasive transcription and rapid death," Nature Communications, Nature, vol. 8(1), pages 1-10, April.
    2. Vitaly Epshtein & Venu Kamarthapu & Katelyn McGary & Vladimir Svetlov & Beatrix Ueberheide & Sergey Proshkin & Alexander Mironov & Evgeny Nudler, 2014. "UvrD facilitates DNA repair by pulling RNA polymerase backwards," Nature, Nature, vol. 505(7483), pages 372-377, January.
    3. Han N. Ho & Antoine M. Oijen & Harshad Ghodke, 2018. "The transcription-repair coupling factor Mfd associates with RNA polymerase in the absence of exogenous damage," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    4. Vitaly Epshtein & Dipak Dutta & Joseph Wade & Evgeny Nudler, 2010. "An allosteric mechanism of Rho-dependent transcription termination," Nature, Nature, vol. 463(7278), pages 245-249, January.
    5. Matthieu D. Lavigne & Dimitris Konstantopoulos & Katerina Z. Ntakou-Zamplara & Anastasios Liakos & Maria Fousteri, 2017. "Global unleashing of transcription elongation waves in response to genotoxic stress restricts somatic mutation rate," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
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    Cited by:

    1. Ya-Mei Ding & Xiao-Xu Pang & Yu Cao & Wei-Ping Zhang & Susanne S. Renner & Da-Yong Zhang & Wei-Ning Bai, 2023. "Genome structure-based Juglandaceae phylogenies contradict alignment-based phylogenies and substitution rates vary with DNA repair genes," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Dmitry Sutormin & Alina Galivondzhyan & Olga Musharova & Dmitrii Travin & Anastasiia Rusanova & Kseniya Obraztsova & Sergei Borukhov & Konstantin Severinov, 2022. "Interaction between transcribing RNA polymerase and topoisomerase I prevents R-loop formation in E. coli," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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