Fig. 1: The two models attempting to explain the control of DNA replication in E. coli.
From: The Escherichia coli replication initiator DnaA is titrated on the chromosome

DnaA negatively auto-regulates its own expression (left). Newly synthesised DnaA is bound by ATP. In the initiator titration model (top), the initiator protein is sequestered by high-affinity DnaA boxes throughout the chromosome. Only when all boxes are saturated, DnaA can bind to low-affinity boxes present on oriC, initiating DNA replication. In the switch model (bottom), DnaA is present in either an ATP-bound, active form, or an ADP-bound, inactive form. Several mechanisms are involved in the switch between the two forms. Once DnaA-ATP accumulates over a specific threshold, it can bind and unwind oriC.