DNA Replication in Bacteria: Control of Initiation

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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.