UvrD facilitates DNA repair by pulling RNA polymerase backwards

Nature. 2014 Jan 16;505(7483):372-7. doi: 10.1038/nature12928. Epub 2014 Jan 8.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA / chemistry
  • DNA / metabolism
  • DNA Damage
  • DNA Helicases / metabolism*
  • DNA Repair*
  • DNA-Directed RNA Polymerases / chemistry
  • DNA-Directed RNA Polymerases / metabolism*
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Escherichia coli Proteins / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Movement*
  • Peptide Elongation Factors / metabolism
  • Protein Binding
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transcriptional Elongation Factors

Substances

  • Escherichia coli Proteins
  • Peptide Elongation Factors
  • Transcription Factors
  • Transcriptional Elongation Factors
  • nusA protein, E coli
  • DNA
  • DNA-Directed RNA Polymerases
  • UvrD protein, E coli
  • DNA Helicases