C-di-AMP reports DNA integrity during sporulation in Bacillus subtilis

Yaara Oppenheimer-Shaanan, Ezequiel Wexselblatt, Jehoshua Katzhendler, Eylon Yavin*, Sigal Ben-Yehuda

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

171 Scopus citations

Abstract

The bacterium Bacillus subtilis produces the DNA integrity scanning protein (DisA), a checkpoint protein that delays sporulation in response to DNA damage. DisA scans the chromosome and pauses at sites of DNA lesions. Structural analysis showed that DisA synthesizes the small molecule cyclic diadenosine monophosphate (c-di-AMP). Here, we demonstrate that the intracellular concentration of c-di-AMP rises markedly at the onset of sporulation in a DisA-dependent manner. Furthermore, exposing sporulating cells to DNA-damaging agents leads to a global decrease in the level of this molecule. This drop was associated with stalled DisA complexes that halt c-di-AMP production and with increased levels of the c-di-AMP-degrading enzyme YybT. Reduced c-di-AMP levels cause a delay in sporulation that can be reversed by external supplementation of the molecule. Thus, c-di-AMP acts as a secondary messenger, coupling DNA integrity with progression of sporulation.

Original languageAmerican English
Pages (from-to)594-601
Number of pages8
JournalEMBO Reports
Volume12
Issue number6
DOIs
StatePublished - Jun 2011

Keywords

  • B. subtilis
  • DNA damage checkpoint
  • DisA
  • c-di-AMP
  • sporulation

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