PMID- 16882985 OWN - NLM STAT- MEDLINE DCOM- 20060925 LR - 20181113 IS - 0890-9369 (Print) IS - 0890-9369 (Linking) VI - 20 IP - 15 DP - 2006 Aug 1 TI - Hda-mediated inactivation of the DnaA protein and dnaA gene autoregulation act in concert to ensure homeostatic maintenance of the Escherichia coli chromosome. PG - 2121-34 AB - 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. FAU - Riber, Leise AU - Riber L AD - Department of Life Sciences and Chemistry, Roskilde University, Denmark. FAU - Olsson, Jan A AU - Olsson JA FAU - Jensen, Rasmus B AU - Jensen RB FAU - Skovgaard, Ole AU - Skovgaard O FAU - Dasgupta, Santanu AU - Dasgupta S FAU - Marinus, Martin G AU - Marinus MG FAU - Lobner-Olesen, Anders AU - Lobner-Olesen A LA - eng GR - R01 GM063790/GM/NIGMS NIH HHS/United States GR - R01 GM063790-04/GM/NIGMS NIH HHS/United States GR - GM63790/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Genes Dev JT - Genes & development JID - 8711660 RN - 0 (Bacterial Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (DnaA protein, Bacteria) RN - 0 (Escherichia coli Proteins) RN - 0 (Trans-Activators) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - EC 3.6.1.- (Adenosine Triphosphatases) RN - EC 3.6.1.- (Hda protein, E coli) SB - IM MH - Adenosine Triphosphatases/*metabolism MH - Adenosine Triphosphate/metabolism MH - Bacterial Proteins/genetics/*metabolism MH - Cell Death MH - *Chromosomes, Bacterial MH - DNA Replication MH - DNA-Binding Proteins/genetics/*metabolism MH - *Escherichia coli/genetics/metabolism MH - Escherichia coli Proteins/*metabolism MH - *Gene Expression Regulation, Bacterial MH - *Homeostasis MH - Replication Origin MH - Trans-Activators PMC - PMC1536062 EDAT- 2006/08/03 09:00 MHDA- 2006/09/26 09:00 PMCR- 2007/02/01 CRDT- 2006/08/03 09:00 PHST- 2006/08/03 09:00 [pubmed] PHST- 2006/09/26 09:00 [medline] PHST- 2006/08/03 09:00 [entrez] PHST- 2007/02/01 00:00 [pmc-release] AID - 20/15/2121 [pii] AID - 10.1101/gad.379506 [doi] PST - ppublish SO - Genes Dev. 2006 Aug 1;20(15):2121-34. doi: 10.1101/gad.379506.