Most bacteria replicate and segregate their DNA concomitantly while growing, before cell division takes place. How bacteria synchronize these different cell cycle events to ensure faithful chromosome inheritance by daughter cells is poorly understood. Here, we identify Cell Cycle Regulator protein interacting with FtsZ (CcrZ) as a conserved and essential protein in pneumococci and related Firmicutes such as Bacillus subtilis and Staphylococcus aureus. CcrZ couples cell division with DNA replication by controlling the activity of the master initiator of DNA replication, DnaA. The absence of CcrZ causes mis-timed and reduced initiation of DNA replication, which subsequently results in aberrant cell division. We show that CcrZ from Streptococcus pneumoniae interacts directly with the cytoskeleton protein FtsZ, which places CcrZ in the middle of the newborn cell where the DnaA-bound origin is positioned. This work uncovers a mechanism for control of the bacterial cell cycle in which CcrZ controls DnaA activity to ensure that the chromosome is replicated at the right time during the cell cycle.

大多数细菌在细胞分裂发生之前，在生长过程中同时复制和分离它们的 DNA。人们对细菌如何同步这些不同的细胞周期事件以确保子细胞忠实的染色体遗传知之甚少。在这里，我们将与 FtsZ (CcrZ) 相互作用的细胞周期调节蛋白鉴定为肺炎球菌和相关厚壁菌门（如枯草芽孢杆菌和金黄色葡萄球菌）中的保守和必需蛋白。CcrZ 通过控制 DNA 复制的主要启动子 DnaA 的活性将细胞分裂与 DNA 复制结合起来。CcrZ 的缺失会导致 DNA 复制的启动时间错误和减少，从而导致细胞分裂异常。我们证明来自肺炎链球菌的 CcrZ直接与细胞骨架蛋白 FtsZ 相互作用，后者将 CcrZ 置于新生细胞的中间，即 DnaA 结合的起源所在的位置。这项工作揭示了一种控制细菌细胞周期的机制，其中 CcrZ 控制 DnaA 活性，以确保染色体在细胞周期中的正确时间复制。