Collier Justine, Shapiro Lucy
Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Quartier UNIL/Sorge, Lausanne, CH 1015, Switzerland.
J Bacteriol. 2009 Sep;191(18):5706-16. doi: 10.1128/JB.00525-09. Epub 2009 Jul 24.
Chromosome replication in Caulobacter crescentus is tightly regulated to ensure that initiation occurs at the right time and only once during the cell cycle. The timing of replication initiation is controlled by both CtrA and DnaA. CtrA binds to and silences the origin. Upon the clearance of CtrA from the cell, the DnaA protein accumulates and allows loading of the replisome at the origin. Here, we identify an additional layer of replication initiation control that is mediated by the HdaA protein. In Escherichia coli, the Hda protein inactivates DnaA after replication initiation. We show that the Caulobacter HdaA homologue is necessary to restrict the initiation of DNA replication to only once per cell cycle and that it dynamically colocalizes with the replisome throughout the cell cycle. Moreover, the transcription of hdaA is directly activated by DnaA, providing a robust feedback regulatory mechanism that adjusts the levels of HdaA to inactivate DnaA.
新月柄杆菌的染色体复制受到严格调控，以确保复制起始在正确的时间发生，并且在细胞周期中仅发生一次。复制起始的时间由CtrA和DnaA共同控制。CtrA结合并使复制起点沉默。当CtrA从细胞中清除后，DnaA蛋白积累，并允许复制体在复制起点加载。在这里，我们发现了由HdaA蛋白介导的另一层复制起始控制。在大肠杆菌中，Hda蛋白在复制起始后使DnaA失活。我们表明，新月柄杆菌的HdaA同源物对于将DNA复制起始限制在每个细胞周期仅一次是必需的，并且它在整个细胞周期中与复制体动态共定位。此外，hdaA的转录直接由DnaA激活，提供了一种强大的反馈调节机制，可调节HdaA的水平以使DnaA失活。
