DNA Replication in Bacteria: Control of Initiation

我们研究的长期目标是了解细胞如何将DNA复制与细胞生长结合起来，并确定控制细菌DNA复制启动速度的分子基础和机制。我们最近发现，启动蛋白DNAA的水平和启动增强剂MIOC启动子的活性受到生长速度的调控；这些调控过程的分子基础将被确定。我们将检查RNA转录是否是所有启动事件实际上都需要的，或者只有在使用遗传和生化方法从缓慢生长速度过渡到快速生长速度时才被细胞使用。对于在ORIC附近引入转录终止和末端稳定抑制信号的突变株，将确定其生长特性和启动时间。这些研究将为mioc启动子区域和转录在启动事件的调节和细胞生长与基因组复制的耦合中的作用提供确凿的证据。

The long term goals of our research are to understand how the cell couples DNA replication with cell growth and to determine the molecular basis and mechanisms involved in controlling the rate of initiation of DNA replication in bacteria. We have recently discovered that levels of the initiator protein, DnaA, and activity of the initiation enhancer, the mioC promoter, are growth rate regulated; the molecular basis of these regulatory processes will be determined. We will examine whether RNA transcription is actually required for all initiation events or only used by the cell when making transitions from slow to fast growth rates using genetic and biochemical approaches. Growth characteristics and timing of initiation will be determined for mutants with transcription termination and telestability inhibitory signals introduced near oriC. These studies will provide definitive evidence for roles of the mioC promoter region and transcription in the regulation of initiation events and in coupling cell growth to genome duplication.