Initiation of DNA Replication at the Chromosomal Origin of E. coli, oriC
The Escherichia coli chromosomal origin consists of a duplex-unwinding region and a region bearing a DNA-bending protein, IHF-binding site, and clusters of binding sites for the initiator protein DnaA. ATP-DnaA molecules form highly organized oligomers in a process stimulated by DiaA, a DnaA-binding protein. The resultant ATP-DnaA complexes promote local unwinding of oriC with the aid of IHF, for which specific interaction of DnaA with the single-stranded DNA is crucial. DnaA complexes also interact with DnaB helicases bound to DnaC loaders, promoting loading of DnaB onto the unwound DNA strands for bidirectional replication. Initiation of replication is strictly regulated during the cell cycle by multiple regulatory systems for oriC and DnaA. The activity of oriC is regulated by its methylation state, whereas that of DnaA depends on the form of the bound nucleotide. ATP-DnaA can be yielded from initiation-inactive ADP-DnaA in a timely manner depending on specific chromosomal DNA elements termed DARS (DnaA-reactivating sequences). After initiation, DnaA-bound ATP is hydrolyzed by two systems, yielding ADP-DnaA. In this review, these and other mechanisms of initiation and its regulation in E. coli are described.
KeywordsoriC DnaA IHF DiaA Hda DARS datA Methylation AAA+ In vitro reconstitution
This work was supported by JSPS KAKENHI Grant Numbers 26291004, 16H00775, 17H03656, and 26650127. I apologize that many papers cannot be cited because of the limitation of space.
- Fingland N, Flåtten I, Downey CD, Fossum-Raunehaug S, Skarstad K, Crooke E (2012) Depletion of acidic phospholipids influences chromosomal replication in Escherichia coli. Microbiology 1:450–466Google Scholar
- Keyamura K, Fujikawa N, Ishida T, Ozaki S, Su’etsugu M, Fujimitsu K, Kagawa W, Yokoyama S, Kurumizaka H, Katayama T (2007) The interaction of DiaA and DnaA regulates the replication cycle in E. coli by directly promoting ATP-DnaA-specific initiation complexes. Genes Dev 21:2083–2099PubMedPubMedCentralCrossRefGoogle Scholar
- Nishida S, Fujimitsu K, Sekimizu K, Ohmura T, Ueda T, Katayama T (2002) A nucleotide switch in the Escherichia coli DnaA protein initiates chromosomal replication: evidence from a mutant DnaA protein defective in regulatory ATP hydrolysis in vitro and in vivo. J Biol Chem 277:14986–14995PubMedCrossRefGoogle Scholar
- Smulczyk-Krawczyszyn A, Jakimowicz D, Ruban-Osmialowska B, Zawilak-Pawlik A, Majka J, Chater K, Zakrzewska-Czerwinska J (2006) Cluster of DnaA boxes involved in regulation of Streptomyces chromosome replication: from in silico to in vivo studies. J Bacteriol 188:6184–6194PubMedPubMedCentralCrossRefGoogle Scholar