Regulating DnaA complex assembly: it is time to fill the gaps

New rounds of bacterial chromosome replication are triggered during each cell division cycle by the initiator protein, DnaA. For precise timing, interactions of DnaA-ATP monomers with the replication origin, oriC, must be carefully regulated during formation of complexes that unwind origin DNA and load replicative helicase. Recent studies in Escherichia coli suggest that high and low affinity DnaA recognition sites are positioned within oriC to direct staged assembly of bacterial pre-replication complexes, with DnaA contacting low affinity sites as it oligomerizes to 'fill the gaps' between high affinity sites. The wide variability of oriC DnaA recognition site patterns seen in nature may reflect myriad gap-filling strategies needed to couple oriC function to the lifestyle of different bacterial types.