Replication initiation proteins regulate a developmental checkpoint in Bacillus subtilis

We identified a signaling pathway that prevents initiation of sporulation i n Bacillus subtillis when replication initiation Is impaired. We isolated m utations that allow a replication initiation mutant (dnaA) to sporulate. Th ese mutations affect a small open reading frame, sda, that was overexpresse d in replication initiation mutants and appears to be directly regulated by DnaA. Mutations in replication initiation genes inhibit the onset of sporu lation by preventing activation of a transcription factor required for spor ulation, Spo0A. Deletion of sda restored activation of Spo0A in replication initiation mutants. Overexpression of sda in otherwise wild-type cells inh ibited activation of Spo0A and sporulation. Purified Sda inhibited a histid ine kinase needed for activation of Spo0A. Our results indicate that contro l of sda by DnaA establishes a checkpoint that inhibits activation of Spo0 and prevents futile attempts to initiate sporulation.