Architecture and inherent robustness of a bacterial cell-cycle control system.

Details

Serval ID
serval:BIB_503439E82C58
Type
Article: article from journal or magazin.
Collection
Publications
Title
Architecture and inherent robustness of a bacterial cell-cycle control system.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Shen X., Collier J., Dill D., Shapiro L., Horowitz M., McAdams H.H.
ISSN
1091-6490
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
105
Number
32
Pages
11340-11345
Language
english
Abstract
A closed-loop control system drives progression of the coupled stalked and swarmer cell cycles of the bacterium Caulobacter crescentus in a near-mechanical step-like fashion. The cell-cycle control has a cyclical genetic circuit composed of four regulatory proteins with tight coupling to processive chromosome replication and cell division subsystems. We report a hybrid simulation of the coupled cell-cycle control system, including asymmetric cell division and responses to external starvation signals, that replicates mRNA and protein concentration patterns and is consistent with observed mutant phenotypes. An asynchronous sequential digital circuit model equivalent to the validated simulation model was created. Formal model-checking analysis of the digital circuit showed that the cell-cycle control is robust to intrinsic stochastic variations in reaction rates and nutrient supply, and that it reliably stops and restarts to accommodate nutrient starvation. Model checking also showed that mechanisms involving methylation-state changes in regulatory promoter regions during DNA replication increase the robustness of the cell-cycle control. The hybrid cell-cycle simulation implementation is inherently extensible and provides a promising approach for development of whole-cell behavioral models that can replicate the observed functionality of the cell and its responses to changing environmental conditions.
Keywords
Caulobacter crescentus, Cell Cycle, Chromosomes, Bacterial, DNA Methylation, DNA Replication, DNA, Bacterial, Models, Biological, Promoter Regions, Genetic, RNA, Bacterial, RNA, Messenger
Pubmed
Web of science
Open Access
Yes
Create date
27/02/2009 15:42
Last modification date
20/08/2019 14:06
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