Department of Developmental Biology, Beckman Center, Stanford University School of Medicine, Stanford, California 94305, USA.
J Bacteriol. 2010 Aug;192(15):3893-902. doi: 10.1128/JB.00468-10. Epub 2010 Jun 4.
Caulobacter crescentus initiates a single round of DNA replication during each cell cycle. Following the initiation of DNA replication, the essential CckA histidine kinase is activated by phosphorylation, which (via the ChpT phosphotransferase) enables the phosphorylation and activation of the CtrA global regulator. CtrA approximately P then blocks the reinitiation of replication while regulating the transcription of a large number of cell cycle-controlled genes. It has been shown that DNA replication serves as a checkpoint for flagellar biosynthesis and cell division and that this checkpoint is mediated by the availability of active CtrA. Because CckA approximately P promotes the activation of CtrA, we addressed the question of what controls the temporal activation of CckA. We found that the initiation of DNA replication is a prerequisite for remodeling the new cell pole, which includes the localization of the DivL protein kinase to that pole and, consequently, the localization, autophosphorylation, and activation of CckA at that pole. Thus, CckA activation is dependent on polar remodeling and a DNA replication initiation checkpoint that is tightly integrated with the polar phospho-signaling cascade governing cell cycle progression.
新月柄杆菌在每个细胞周期中只启动一轮 DNA 复制。在 DNA 复制起始后，必需的 CckA 组氨酸激酶被磷酸化激活，这（通过 ChpT 磷酸转移酶）使 CtrA 全局调节剂的磷酸化和激活成为可能。CtrA 随后大约 P 阻止复制的重新起始，同时调节大量细胞周期控制基因的转录。已经表明，DNA 复制作为鞭毛生物合成和细胞分裂的检查点，并且该检查点由活性 CtrA 的可用性介导。因为 CckA 大约 P 促进 CtrA 的激活，所以我们解决了控制 CckA 时间激活的问题。我们发现 DNA 复制的起始是新细胞极重塑的先决条件，其中包括 DivL 蛋白激酶在该极的定位，以及由此导致的 CckA 在该极的定位、自磷酸化和激活。因此，CckA 的激活依赖于极性重塑和 DNA 复制起始检查点，该检查点与控制细胞周期进程的极性磷酸信号级联紧密集成。
