Replication initiation at the Escherichia coli chromosomal origin

To initiate DNA replication, DnaA recognizes and binds to specific sequences within the Escherichia coli chromosomal origin (oriC), and then unwinds a region within oriC. Next, DnaA interacts with DnaB helicase in loading the DnaB–DnaC complex on each separated strand. Primer formation by primase (DnaG) induces the dissociation of DnaC from DnaB, which involves the hydrolysis of ATP bound to DnaC. Recent evidence indicates that DnaC acts as a checkpoint in the transition from initiation to the elongation stage of DNA replication. Freed from DnaC, DnaB helicase unwinds the parental duplex DNA while interacting the cellular replicase, DNA polymerase III holoenzyme, and primase as it intermittently forms primers that are extended by the replicase in duplicating the chromosome.

► DnaA interacts with DnaA boxes, I-sites, and τ-sites in oriC.
► At oriC, DnaA loads DnaB helicase from the DnaB–DnaC complex.
► Assembly of the replication fork machinery is a step-wise process.
► Primer formation by primase (DnaG) induces the dissociation of DnaC from DnaB.
► DnaC acts as a checkpoint in initiation.