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Cell size at S phase initiation: an emergent property of the G1/S network.

Barberis M, Klipp E, Vanoni M, Alberghina L - PLoS Comput. Biol. (2007)

Bottom Line: The model was tested by simulation in several genetic and nutritional setups and was found to be neatly consistent with experimental data.To estimate PS, the authors developed a hybrid model including a probabilistic component for firing of DNA replication origins.Sensitivity analysis of PS provides a novel relevant conclusion: PS is an emergent property of the G1 to S network that strongly depends on growth rate.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.

ABSTRACT
The eukaryotic cell cycle is the repeated sequence of events that enable the division of a cell into two daughter cells. It is divided into four phases: G1, S, G2, and M. Passage through the cell cycle is strictly regulated by a molecular interaction network, which involves the periodic synthesis and destruction of cyclins that bind and activate cyclin-dependent kinases that are present in nonlimiting amounts. Cyclin-dependent kinase inhibitors contribute to cell cycle control. Budding yeast is an established model organism for cell cycle studies, and several mathematical models have been proposed for its cell cycle. An area of major relevance in cell cycle control is the G1 to S transition. In any given growth condition, it is characterized by the requirement of a specific, critical cell size, PS, to enter S phase. The molecular basis of this control is still under discussion. The authors report a mathematical model of the G1 to S network that newly takes into account nucleo/cytoplasmic localization, the role of the cyclin-dependent kinase Sic1 in facilitating nuclear import of its cognate Cdk1-Clb5, Whi5 control, and carbon source regulation of Sic1 and Sic1-containing complexes. The model was implemented by a set of ordinary differential equations that describe the temporal change of the concentration of the involved proteins and protein complexes. The model was tested by simulation in several genetic and nutritional setups and was found to be neatly consistent with experimental data. To estimate PS, the authors developed a hybrid model including a probabilistic component for firing of DNA replication origins. Sensitivity analysis of PS provides a novel relevant conclusion: PS is an emergent property of the G1 to S network that strongly depends on growth rate.

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Effect of Signaling Pathway Activation on Cell Cycle ProgressionThe effects of the pheromone pathway (A,B) and the stress-response Hog1-dependent pathway (C,D) on Cdk1-Cln1,2cyt (left panels) and Cdk1-Clb5,6nuc (right panels) are reported. In each panel, basal wild-type is shown in black and “activated pathways” as a dotted line.
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pcbi-0030064-g006: Effect of Signaling Pathway Activation on Cell Cycle ProgressionThe effects of the pheromone pathway (A,B) and the stress-response Hog1-dependent pathway (C,D) on Cdk1-Cln1,2cyt (left panels) and Cdk1-Clb5,6nuc (right panels) are reported. In each panel, basal wild-type is shown in black and “activated pathways” as a dotted line.

Mentions: The core of the cycle machinery has to cope with intracellular and extracellular signals that, ultimately, lead to an alteration in expression of cell cycle–regulatory proteins. Thus, we simulated the effect of signaling through the pheromone pathway and the stress-response Hog1-dependent pathway—whose modeling [21,49] lies outside the scope of this paper—by altering parameters of one or more of the biochemical reactions included in the G1/S transition network that are known to be modified by alterations in the signaling pathway (Figure 6 and Table S3).


Cell size at S phase initiation: an emergent property of the G1/S network.

Barberis M, Klipp E, Vanoni M, Alberghina L - PLoS Comput. Biol. (2007)

Effect of Signaling Pathway Activation on Cell Cycle ProgressionThe effects of the pheromone pathway (A,B) and the stress-response Hog1-dependent pathway (C,D) on Cdk1-Cln1,2cyt (left panels) and Cdk1-Clb5,6nuc (right panels) are reported. In each panel, basal wild-type is shown in black and “activated pathways” as a dotted line.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1851985&req=5

pcbi-0030064-g006: Effect of Signaling Pathway Activation on Cell Cycle ProgressionThe effects of the pheromone pathway (A,B) and the stress-response Hog1-dependent pathway (C,D) on Cdk1-Cln1,2cyt (left panels) and Cdk1-Clb5,6nuc (right panels) are reported. In each panel, basal wild-type is shown in black and “activated pathways” as a dotted line.
Mentions: The core of the cycle machinery has to cope with intracellular and extracellular signals that, ultimately, lead to an alteration in expression of cell cycle–regulatory proteins. Thus, we simulated the effect of signaling through the pheromone pathway and the stress-response Hog1-dependent pathway—whose modeling [21,49] lies outside the scope of this paper—by altering parameters of one or more of the biochemical reactions included in the G1/S transition network that are known to be modified by alterations in the signaling pathway (Figure 6 and Table S3).

Bottom Line: The model was tested by simulation in several genetic and nutritional setups and was found to be neatly consistent with experimental data.To estimate PS, the authors developed a hybrid model including a probabilistic component for firing of DNA replication origins.Sensitivity analysis of PS provides a novel relevant conclusion: PS is an emergent property of the G1 to S network that strongly depends on growth rate.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.

ABSTRACT
The eukaryotic cell cycle is the repeated sequence of events that enable the division of a cell into two daughter cells. It is divided into four phases: G1, S, G2, and M. Passage through the cell cycle is strictly regulated by a molecular interaction network, which involves the periodic synthesis and destruction of cyclins that bind and activate cyclin-dependent kinases that are present in nonlimiting amounts. Cyclin-dependent kinase inhibitors contribute to cell cycle control. Budding yeast is an established model organism for cell cycle studies, and several mathematical models have been proposed for its cell cycle. An area of major relevance in cell cycle control is the G1 to S transition. In any given growth condition, it is characterized by the requirement of a specific, critical cell size, PS, to enter S phase. The molecular basis of this control is still under discussion. The authors report a mathematical model of the G1 to S network that newly takes into account nucleo/cytoplasmic localization, the role of the cyclin-dependent kinase Sic1 in facilitating nuclear import of its cognate Cdk1-Clb5, Whi5 control, and carbon source regulation of Sic1 and Sic1-containing complexes. The model was implemented by a set of ordinary differential equations that describe the temporal change of the concentration of the involved proteins and protein complexes. The model was tested by simulation in several genetic and nutritional setups and was found to be neatly consistent with experimental data. To estimate PS, the authors developed a hybrid model including a probabilistic component for firing of DNA replication origins. Sensitivity analysis of PS provides a novel relevant conclusion: PS is an emergent property of the G1 to S network that strongly depends on growth rate.

Show MeSH
Related in: MedlinePlus