Initiation of DNA replication in bacteria: Analysis of an autorepressor control model

The precise mechanism by which the initiation of chromosome replication in bacteria is controlled has not yet been established, and several theoretical models have been proposed in an attempt to provide a conceptual framework for the accumulated experimental evidence. The present article contains a detailed quantitative analysis, using computer simulation, of the control model first put forward schematically by Sompayrac & Maaløe in 1973, in which a single operon codes for both the initiator protein and an autorepressor. By comparing the predictions of the model with what is known about the physiology and molecular biology of Escherichia coli under different growth conditions, we are able to delineate the characteristics that such a control system would need to possess in order to be capable of regulating chromosome replication: the control operon has to lie fairly near the origin of replication and contain a moderate to strong promoter and an operator that competes for its repressor with other equally specific binding sites along the chromosome in an interaction that is somewhat weaker than usual; in addition, the messenger molecules encoded for by the repressor gene must have a relatively ineffective ribosome binding site and not too long a halflife.