RNA polymerase modulators and DNA repair activities resolve conflicts between DNA replication and transcription

Mol Cell. 2005 Jul 22;19(2):247-58. doi: 10.1016/j.molcel.2005.06.004.


Organisms rely on close interplay between DNA replication, recombination, and repair to secure transmission of the genome. In rapidly dividing cells, there is also great pressure for transcription, which may induce conflict with replication. We investigated the potential for conflict in bacterial cells, where there is no temporal separation of these processes. Eliminating the stringent response regulators ppGpp and DksA or the GreA and Mfd proteins, which revive or dislodge stalled transcription complexes, and especially combinations of these factors, is shown to severely reduce viability when DNA repair is also compromised. Both ppGpp and certain RNA polymerase (RNAP) mutations reduce accumulation of backed-up arrays of stalled transcription complexes. We propose these arrays are formidable obstacles to replication that are normally kept in check in wild-type cells by ppGpp, DksA, GreA, and Mfd. When arrays do obstruct replication, the consequences are resolved by one of the many pathways available to rescue stalled forks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Repair / genetics
  • DNA Repair / physiology*
  • DNA Repair / radiation effects
  • DNA Replication / genetics*
  • DNA Replication / physiology
  • DNA Replication / radiation effects
  • DNA-Directed RNA Polymerases / genetics*
  • DNA-Directed RNA Polymerases / physiology*
  • DNA-Directed RNA Polymerases / radiation effects
  • Escherichia coli K12 / growth & development
  • Escherichia coli K12 / metabolism
  • Escherichia coli K12 / radiation effects
  • Guanosine Tetraphosphate / metabolism
  • Mutation
  • Time Factors
  • Transcription, Genetic / genetics*
  • Transcription, Genetic / physiology
  • Transcription, Genetic / radiation effects
  • Ultraviolet Rays


  • Guanosine Tetraphosphate
  • DNA-Directed RNA Polymerases