Article | Published:

UvrD facilitates DNA repair by pulling RNA polymerase backwards

Nature volume 505, pages 372377 (16 January 2014) | Download Citation

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.

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Acknowledgements

We thank D. Jeruzalmi for materials. This work was supported by the Russian Foundation for Basic Research (A.M.) and the NIH, BGRF, Dynasty foundation and by the Howard Hughes Medical Institute (E.N.).

Author information

Author notes

    • Vitaly Epshtein
    •  & Venu Kamarthapu

    These authors contributed equally to this work.

Affiliations

  1. Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA

    • Vitaly Epshtein
    • , Venu Kamarthapu
    • , Katelyn McGary
    • , Vladimir Svetlov
    • , Beatrix Ueberheide
    •  & Evgeny Nudler
  2. Howard Hughes Medical Institute, New York University School of Medicine, New York, New York 10016, USA

    • Venu Kamarthapu
    •  & Evgeny Nudler
  3. State Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow 117545, Russia

    • Sergey Proshkin
    •  & Alexander Mironov
  4. Engelhardt Institute of Molecular Biology, Russian Academy of Science, Moscow 119991, Russia

    • Alexander Mironov

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Contributions

V.E., V.K., K.M., V.S., B.U., S.P. and A.M. conducted the experimental work, discussed the results and commented on the manuscript. E.N. designed the study and wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Evgeny Nudler.

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https://doi.org/10.1038/nature12928

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