Title
Cell Size At S Phase Initiation: An Emergent Property Of The G(1)/S Network
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: G(1), S, G(2), 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 G(1) 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 G(1) 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 P-S, the authors developed a hybrid model including a probabilistic component for firing of DNA replication origins. Sensitivity analysis of P-S provides a novel relevant conclusion: P-S is an emergent property of the G(1) to S network that strongly depends on growth rate.
Year
DOI
Venue
2007
10.1371/journal.pcbi.0030064
PLOS COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
emergent properties,cell cycle,signal transduction,computer simulation
Cell division,Biology,S-phase-promoting factor,Cell biology,Interaction network,Saccharomyces cerevisiae,Cell cycle,Bioinformatics,DNA replication,Cell Cycle Protein,Sic1
Journal
Volume
Issue
ISSN
3
4
1553-7358
Citations 
PageRank 
References 
10
2.18
1
Authors
4
Name
Order
Citations
PageRank
Matteo Barberis1314.05
Edda Klipp228319.57
Marco Vanoni3768.30
Lilia Alberghina4859.41