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PLoS Genet. 2015 Jul 2;11(7):e1005342. doi: 10.1371/journal.pgen.1005342. eCollection 2015 Jul.

Nutritional Control of DNA Replication Initiation through the Proteolysis and Regulated Translation of DnaA.

Author information

1
LOEWE Center for Synthetic Microbiology, Philipps University Marburg, Marburg, Germany; Max Planck Institute for Terrestrial Microbiology, Marburg, Germany.
2
LOEWE Center for Synthetic Microbiology, Philipps University Marburg, Marburg, Germany.
3
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
4
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
5
LOEWE Center for Synthetic Microbiology, Philipps University Marburg, Marburg, Germany; Department of Biology, Philipps University Marburg, Marburg, Germany.

Abstract

Bacteria can arrest their own growth and proliferation upon nutrient depletion and under various stressful conditions to ensure their survival. However, the molecular mechanisms responsible for suppressing growth and arresting the cell cycle under such conditions remain incompletely understood. Here, we identify post-transcriptional mechanisms that help enforce a cell-cycle arrest in Caulobacter crescentus following nutrient limitation and during entry into stationary phase by limiting the accumulation of DnaA, the conserved replication initiator protein. DnaA is rapidly degraded by the Lon protease following nutrient limitation. However, the rate of DnaA degradation is not significantly altered by changes in nutrient availability. Instead, we demonstrate that decreased nutrient availability downregulates dnaA translation by a mechanism involving the 5' untranslated leader region of the dnaA transcript; Lon-dependent proteolysis of DnaA then outpaces synthesis, leading to the elimination of DnaA and the arrest of DNA replication. Our results demonstrate how regulated translation and constitutive degradation provide cells a means of precisely and rapidly modulating the concentration of key regulatory proteins in response to environmental inputs.

PMID:
26134530
PMCID:
PMC4489657
DOI:
10.1371/journal.pgen.1005342
[Indexed for MEDLINE]
Free PMC Article

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