DNA replication, the bacterial cell cycle, and cell growth.

The coupling of replication to the cell cycle and cell growth involves events that occur at oriC. Immediately after initiation, there is an eclipse phase during which reinitiation from the newly synthesized origins is prevented. GATC sites in oriC remain in a hemimethylated state longer than other sites because of their association with the outer membrane, which prevents DnaA from binding and activating additional rounds of initiation. After the origins are methylated and released from the outer membrane, the concentration of newly synthesized DnaA and the activation of oriC by transcription from the nearby mioC and gid promoters determine when the next rounds of replication initiate. If growth rate is reduced, the synthesis of (p)ppGpp will increase, and this will lead to a decrease in dnaA, mioC, and gid transcription. On the other hand, if growth rate is increased by access to a tasty meal, synthesis of (p)ppGpp will decrease, expression of dnaA, mioC, and gid genes will increase, and a shortening of the interinitiation time will result. The participation of all these control features ensures rapid and precise coordination of DNA replication with cell growth.