Dividing cells must coordinate cell cycle events to ensure genetic sta
bility. Here we identify an essential two-component signal transductio
n protein that controls multiple events in the Caulobacter cell cycle,
including cell division, stalk synthesis, and cell cycle-specific tra
nscription. This protein, CtrA, is homologous to response regulator tr
anscription factors and controls transcription from a group of cell cy
cle-regulated promoters critical for DNA replication, DNA methylation,
and flagellar biogenesis. CtrA activity in the cell cycle is controll
ed both transcriptionally and by phosphorylation. As purified CtrA bin
ds an essential DNA sequence motif found within its target promoters,
we propose that CtrA acts in a phosphorelay signal transduction system
to control bacterial cell cycle events directly at the transcriptiona
l level.