dnaA

DnaA is the initiator protein of chromosomal DNA replication in most bacteria. It is an AAA+ ATPase that binds to the origin of replication, oriC, at multiple DnaA box sequences. In its ATP-bound form, DnaA assembles into oligomeric complexes on oriC and induces local unwinding of the adjacent DNA unwinding element (DUE), creating a ready platform for replication to begin.

The ATP-bound DnaA complex promotes recruitment of the replicative helicase DnaB with the help of the helicase loader DnaC (in Escherichia coli and some other bacteria). DnaA-ATP activity drives the initial DNA strand separation and the stable loading of DnaB helicases onto the parental strands. DnaA-ADP is largely inactive for initiation, and hydrolysis of ATP to ADP leads to disassembly and reduced ability to reopen oriC in subsequent cycles.

Regulation of DnaA activity ensures proper timing and one-round initiation per cell cycle. Regulatory inactivation of DnaA (RIDA) promotes ATP hydrolysis by DnaA after initiation, often involving the Hda protein. SeqA binds hemimethylated oriC after replication, temporarily sequestering the origin and blocking reinitiation. The datA locus also modulates DnaA ATP/ADP status by promoting ATP hydrolysis. Additional species-specific factors, including nucleoid-associated proteins such as IHF and FIS, influence the architecture of oriC and the efficiency of initiation.

DnaA is essential for bacterial viability, with oriC architecture and DnaA box organization varying among species. Its activity integrates cellular signals to coordinate replication initiation with growth and division.