Multiple regulatory systems coordinate DNA replication with cell growth in Bacillus subtilis

Heath Murray, Alan Koh

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

In many bacteria the rate of DNA replication is linked with cellular physiology to ensure that genome duplication is coordinated with growth. Nutrient-mediated growth rate control of DNA replication initiation has been appreciated for decades, however the mechanism(s) that connects these cell cycle activities has eluded understanding. In order to help address this fundamental question we have investigated regulation of DNA replication in the model organism Bacillus subtilis. Contrary to the prevailing view we find that changes in DnaA protein level are not sufficient to account for nutrient-mediated growth rate control of DNA replication initiation, although this regulation does require both DnaA and the endogenous replication origin. We go on to report connections between DNA replication and several essential cellular activities required for rapid bacterial growth, including respiration, central carbon metabolism, fatty acid synthesis, phospholipid synthesis, and protein synthesis. Unexpectedly, the results indicate that multiple regulatory systems are involved in coordinating DNA replication with cell physiology, with some of the regulatory systems targeting oriC while others act in a oriC-independent manner. We propose that distinct regulatory systems are utilized to control DNA replication in response to diverse physiological and chemical changes.

Original languageEnglish
Article numbere1004731
JournalPlos Genetics
Volume10
Issue number10
DOIs
Publication statusPublished - 23 Oct 2014

Keywords

  • Bacillus subtilis
  • Cell Cycle
  • Cell Division
  • Cell Growth Processes
  • DNA Replication
  • DNA-Binding Proteins
  • Gene Expression Regulation, Bacterial
  • Origin Recognition Complex
  • Xylose
  • Journal Article
  • Research Support, Non-U.S. Gov't

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