CtrA mediates a DNA replication checkpoint that prevents cell division in Caulobacter crescentus

Coordination of DNA replication and cell division is essential in order to ensure that progeny cells inherit a full copy of the genome, Caulobacter crescentus divides asymmetrically to produce a non-replicating swarmer cell and a replicating stalked cell. The global response regulator CtrA coordinates DNA replication and cell division by repressing replication initiation and transcription of the early cell division gene ftsZ in swarmer cells. We show that CtrA also mediates a DNA replication checkpoint of cell division by regulating the late cell division genes ftsQ and ftsA. CtrA activates transcription of the P-QA promoter that co-transcribes ftsQA, thus regulating the ordered expression of early and late cell division proteins. Cells inhibited for DNA replication are unable to complete cell division. We show that CtrA is not synthesized in pre-divisional cells in which replication has been inhibited, preventing the transcription of P-QA and cell division. Replication inhibition prevents the activation of the ctrA P2 promoter, which normally depends on CtrA phosphorylation. This suggests the possibility that CtrA phosphorylation may be affected by replication inhibition.