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UvrD facilitates DNA repair by pulling RNA polymerase backwards

Author

Listed:
  • Vitaly Epshtein

    (New York University School of Medicine)

  • Venu Kamarthapu

    (New York University School of Medicine
    Howard Hughes Medical Institute, New York University School of Medicine)

  • Katelyn McGary

    (New York University School of Medicine)

  • Vladimir Svetlov

    (New York University School of Medicine)

  • Beatrix Ueberheide

    (New York University School of Medicine)

  • Sergey Proshkin

    (State Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow 117545, Russia)

  • Alexander Mironov

    (State Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow 117545, Russia
    Engelhardt Institute of Molecular Biology, Russian Academy of Science, Moscow 119991, Russia)

  • Evgeny Nudler

    (New York University School of Medicine
    Howard Hughes Medical Institute, New York University School of Medicine)

Abstract

UvrD helicase is required for nucleotide excision repair, although its role in this process is not well defined. Here we show that Escherichia coli UvrD binds RNA polymerase during transcription elongation and, using its helicase/translocase activity, forces RNA polymerase to slide backward along DNA. By inducing backtracking, UvrD exposes DNA lesions shielded by blocked RNA polymerase, allowing nucleotide excision repair enzymes to gain access to sites of damage. Our results establish UvrD as a bona fide transcription elongation factor that contributes to genomic integrity by resolving conflicts between transcription and DNA repair complexes. Furthermore, we show that the elongation factor NusA cooperates with UvrD in coupling transcription to DNA repair by promoting backtracking and recruiting nucleotide excision repair enzymes to exposed lesions. Because backtracking is a shared feature of all cellular RNA polymerases, we propose that this mechanism enables RNA polymerases to function as global DNA damage scanners in bacteria and eukaryotes.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:nature:v:505:y:2014:i:7483:d:10.1038_nature12928
    DOI: 10.1038/nature12928
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    Cited by:

    1. 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.
    2. Sean P. Carney & Wen Ma & Kevin D. Whitley & Haifeng Jia & Timothy M. Lohman & Zaida Luthey-Schulten & Yann R. Chemla, 2021. "Kinetic and structural mechanism for DNA unwinding by a non-hexameric helicase," Nature Communications, Nature, vol. 12(1), pages 1-14, December.

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