Coupling chromosomal replication to cell growth by the initiator protein DnaA in Escherichia coli.

The initiation of chromosomal replication is strictly controlled during the cell cycle. Its frequency needs to be well-matched to the proliferation rate. In many bacteria, DnaA is the critical mediator in the regulation of replication initiation. In this work, the initiation probability is deduced based on the distribution of DnaA boxes at oriC in Escherichia coli. Taking into account more details, we develop a dynamic model to describe the oscillation of DnaA accompanied with the cell cycles. Our simulations show that the regulation of DnaA couples chromosomal replication to cell growth. We also discuss effects of other factors on DnaA oscillation. We propose that RNA polymerase is one of the candidates for harmonizing chromosomal replication and cell growth by adjusting dnaA transcriptional activity.