The transcription fidelity factor GreA impedes DNA break repair

Nature. 2017 Oct 12;550(7675):214-218. doi: 10.1038/nature23907. Epub 2017 Oct 4.

Abstract

Homologous recombination repairs DNA double-strand breaks and must function even on actively transcribed DNA. Because break repair prevents chromosome loss, the completion of repair is expected to outweigh the transcription of broken templates. However, the interplay between DNA break repair and transcription processivity is unclear. Here we show that the transcription factor GreA inhibits break repair in Escherichia coli. GreA restarts backtracked RNA polymerase and hence promotes transcription fidelity. We report that removal of GreA results in markedly enhanced break repair via the classic RecBCD-RecA pathway. Using a deep-sequencing method to measure chromosomal exonucleolytic degradation, we demonstrate that the absence of GreA limits RecBCD-mediated resection. Our findings suggest that increased RNA polymerase backtracking promotes break repair by instigating RecA loading by RecBCD, without the influence of canonical Chi signals. The idea that backtracked RNA polymerase can stimulate recombination presents a DNA transaction conundrum: a transcription fidelity factor that compromises genomic integrity.

Publication types

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

MeSH terms

  • DNA Breaks, Double-Stranded
  • DNA Repair*
  • DNA-Directed RNA Polymerases / metabolism
  • Escherichia coli / enzymology
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / metabolism*
  • Exodeoxyribonuclease V / metabolism
  • Protein Binding
  • Rec A Recombinases / metabolism
  • Transcription Factors / metabolism*
  • Transcription, Genetic*

Substances

  • Escherichia coli Proteins
  • GreA protein, E coli
  • Transcription Factors
  • Rec A Recombinases
  • DNA-Directed RNA Polymerases
  • Exodeoxyribonuclease V
  • exodeoxyribonuclease V, E coli