Inactivation of Escherichia coli DnaA protein by DNA polymerase III and negative regulations for initiation of chromosomal replication

Genetic and biochemical evidence indicates that initiation of chromosomal r eplication in Escherichia coli occurs in a nucleoprotein complex at the rep lication origin (oriC) formed with DnaA protein. The frequency of initiatio n at oriC is tightly regulated to only once per chromosome per cell cycle. To prevent untimely, extra initiations, negative control for initiation is indispensable. Recently, we found that the function of the initiator protei n, DnaA, is controlled by DNA polymerase III holoenzyme, the replicase of t he chromosome. The ATP-bound form of DnaA protein, an active form for initi ation, is efficiently converted to the ADP bound form, an inactive form, si nce a subunit of the polymerase loaded on DNA (beta subunit sliding clamp) stimulates hydrolysis of ATP bound to DnaA protein. Comparison of this syst em, RIDA (regulatory inactivation of DnaA), with other systems for negative regulation of initiation is included in this review, and the roles of thes e systems for concerted control for initiation during the cell cycle are di scussed. (C) 1999 Societe francaise de biochimie et biologie moleculaire/Ed itions scientifiques et medicales Elsevier SAS.