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 cr escentus divides asymmetrically to produce a non-replicating swarmer cell a nd a replicating stalked cell. The global response regulator CtrA coordinat es DNA replication and cell division by repressing replication initiation a nd 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 tr anscription of the P-QA promoter that co-transcribes ftsQA, thus regulating the ordered expression of early and late cell division proteins. Cells inh ibited for DNA replication are unable to complete cell division. We show th at CtrA is not synthesized in pre-divisional cells in which replication has been inhibited, preventing the transcription of P-QA and cell division. Re plication inhibition prevents the activation of the ctrA P2 promoter, which normally depends on CtrA phosphorylation. This suggests the possibility th at CtrA phosphorylation may be affected by replication inhibition.