Hda-mediated inactivation of the DnaA protein and dnaA gene autoregulation act in concert to ensure homeostatic maintenance of the Escherichia coli chromosome

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date


Document Type



Adenosine Triphosphatases; Adenosine Triphosphate; Bacterial Proteins; Cell Death; *Chromosomes, Bacterial; DNA Replication; DNA-Binding Proteins; *Escherichia coli; Escherichia coli Proteins; *Gene Expression Regulation, Bacterial; *Homeostasis; Replication Origin; Trans-Activators


Biochemistry, Biophysics, and Structural Biology | Pharmacology, Toxicology and Environmental Health


Initiation of DNA replication in Eschericia coli requires the ATP-bound form of the DnaA protein. The conversion of DnaA-ATP to DnaA-ADP is facilitated by a complex of DnaA, Hda (homologous to DnaA), and DNA-loaded beta-clamp proteins in a process termed RIDA (regulatory inactivation of DnaA). Hda-deficient cells initiate replication at each origin mainly once per cell cycle, and the rare reinitiation events never coincide with the end of the origin sequestration period. Therefore, RIDA is not the predominant mechanism to prevent immediate reinitiation from oriC. The cellular level of Hda correlated directly with dnaA gene expression such that Hda deficiency led to reduced dnaA gene expression, and overproduction of Hda led to DnaA overproduction. Hda-deficient cells were very sensitive to variations in the cellular level of DnaA, and DnaA overproduction led to uncontrolled initiation of replication from oriC, causing severe growth retardation or cell death. Based on these observations, we propose that both RIDA and dnaA gene autoregulation are required as homeostatic mechanisms to ensure that initiation of replication occurs at the same time relative to cell mass in each cell cycle.

DOI of Published Version



Genes Dev. 2006 Aug 1;20(15):2121-34. Link to article on publisher's site

Journal/Book/Conference Title

Genes and development

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Link to Article in PubMed

PubMed ID