ppGpp couples transcription to DNA repair in E. coli

Science. 2016 May 20;352(6288):993-6. doi: 10.1126/science.aad6945.

Abstract

The small molecule alarmone (p)ppGpp mediates bacterial adaptation to nutrient deprivation by altering the initiation properties of RNA polymerase (RNAP). ppGpp is generated in Escherichia coli by two related enzymes, RelA and SpoT. We show that ppGpp is robustly, but transiently, induced in response to DNA damage and is required for efficient nucleotide excision DNA repair (NER). This explains why relA-spoT-deficient cells are sensitive to diverse genotoxic agents and ultraviolet radiation, whereas ppGpp induction renders them more resistant to such challenges. The mechanism of DNA protection by ppGpp involves promotion of UvrD-mediated RNAP backtracking. By rendering RNAP backtracking-prone, ppGpp couples transcription to DNA repair and prompts transitions between repair and recovery states.

Publication types

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

MeSH terms

  • DNA Damage
  • DNA Helicases / metabolism
  • DNA Repair*
  • DNA-Directed RNA Polymerases / genetics
  • DNA-Directed RNA Polymerases / metabolism
  • Escherichia coli / genetics*
  • Escherichia coli Proteins / metabolism
  • Guanosine Tetraphosphate / metabolism*
  • Transcription, Genetic*

Substances

  • Escherichia coli Proteins
  • Guanosine Tetraphosphate
  • DNA-Directed RNA Polymerases
  • UvrD protein, E coli
  • DNA Helicases