Wortinger M, Sackett M J, Brun Y V
Department of Biology and Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.
EMBO J. 2000 Sep 1;19(17):4503-12. doi: 10.1093/emboj/19.17.4503.
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.
DNA复制与细胞分裂的协调对于确保子代细胞继承完整的基因组至关重要。新月柄杆菌进行不对称分裂，产生一个不进行复制的游动细胞和一个进行复制的柄细胞。全局响应调节因子CtrA通过抑制游动细胞中的复制起始和早期细胞分裂基因ftsZ的转录来协调DNA复制和细胞分裂。我们发现，CtrA还通过调节晚期细胞分裂基因ftsQ和ftsA来介导细胞分裂的DNA复制检查点。CtrA激活共同转录ftsQA的P(QA)启动子的转录，从而调节早期和晚期细胞分裂蛋白的有序表达。DNA复制受到抑制的细胞无法完成细胞分裂。我们发现，在复制受到抑制的分裂前细胞中不合成CtrA，从而阻止P(QA)的转录和细胞分裂。复制抑制会阻止ctrA P2启动子的激活，该启动子通常依赖于CtrA磷酸化。这表明CtrA磷酸化可能受复制抑制影响。
