The transcriptional regulation and target binding site of the sporulation kinase inhibitor, Sda
Histidine kinase signaling pathways are a widespread type of protein kinase signaling pathway that allow cells to sense and respond to changes in the environment. One important feature of these systems is that secondary signals can be integrated into the pathway to modulate the cellular response. The process of sporulation in the Gram-positive bacterium, Bacillus subtilis, is regulated by a histidine kinase signaling pathway. When cells are primed to sporulate but incur blocks to DNA replication, the endogenous histidine kinase inhibitor, Sda, delays sporulation until the replication blocks are relieved by inhibiting the activity of the sporulation kinases, KinA and KinB. In this work, we show how transcription of sda is convergently regulated by the recA-dependent SOS response and the replication initiation factor DnaA in response to replication defects. To further our understanding of how Sda recognizes and inhibits its targets, we identified residues of KinA that are required for Sda binding and inhibition. Finally, we identified factors that contribute to chromosome segregation defects when cells are induced to sporulate prematurely. Together, these studies demonstrate how an endogenous histidine kinase inhibitor is activated by blocks to DNA replication and subsequently inhibits cells from sporulating by binding a hydrophobic surface on its target.