Replication initiation proteins regulate a developmental checkpoint in Bacillus subtilis

Cell. 2001 Jan 26;104(2):269-79. doi: 10.1016/s0092-8674(01)00211-2.


We identified a signaling pathway that prevents initiation of sporulation in Bacillus subtilis when replication initiation is impaired. We isolated mutations that allow a replication initiation mutant (dnaA) to sporulate. These mutations affect a small open reading frame, sda, that was overexpressed in replication initiation mutants and appears to be directly regulated by DnaA. Mutations in replication initiation genes inhibit the onset of sporulation by preventing activation of a transcription factor required for sporulation, Spo0A. Deletion of sda restored activation of Spo0A in replication initiation mutants. Overexpression of sda in otherwise wild-type cells inhibited activation of Spo0A and sporulation. Purified Sda inhibited a histidine kinase needed for activation of Spo0A. Our results indicate that control of sda by DnaA establishes a checkpoint that inhibits activation of Spo0A and prevents futile attempts to initiate sporulation.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Autoradiography
  • Bacillus subtilis / genetics
  • Bacillus subtilis / physiology*
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Base Sequence
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • DNA Replication / physiology*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • DnaB Helicases
  • Electrophoresis, Polyacrylamide Gel
  • Histidine Kinase
  • Molecular Sequence Data
  • Mutation
  • Open Reading Frames*
  • Protein Kinase Inhibitors
  • Protein Kinases / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Signal Transduction
  • Spores, Bacterial / genetics
  • Spores, Bacterial / metabolism
  • Suppression, Genetic
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Bacterial Proteins
  • DNA-Binding Proteins
  • DnaA protein, Bacteria
  • Protein Kinase Inhibitors
  • Recombinant Fusion Proteins
  • Spo0A protein, Bacillus subtilis
  • Spo0F protein, Bacillus subtilis
  • Transcription Factors
  • kinA protein, Bacillus subtilis
  • suppressor of DnaA, Bacillus subtilis
  • Protein Kinases
  • Histidine Kinase
  • DNA Helicases
  • DnaB Helicases