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Chen2004 - Cell Cycle Regulation


ABSTRACT: Chen2004 - Cell Cycle Regulation This is a hypothetical model of cell cycle that describes the molecular mechanism for regulating DNA synthesis, bud emergence, mitosis, and cell division in budding yeast. This model is described in the article: Integrative analysis of cell cycle control in budding yeast. Chen KC, Calzone L, Csikasz-Nagy A, Cross FR, Novak B, Tyson JJ Mol. Biol. Cell. [2004 Aug; Volume: 15 (Issue: 8 )] Page info: 3841-62 Abstract: The adaptive responses of a living cell to internal and external signals are controlled by networks of proteins whose interactions are so complex that the functional integration of the network cannot be comprehended by intuitive reasoning alone. Mathematical modeling, based on biochemical rate equations, provides a rigorous and reliable tool for unraveling the complexities of molecular regulatory networks. The budding yeast cell cycle is a challenging test case for this approach, because the control system is known in exquisite detail and its function is constrained by the phenotypic properties of >100 genetically engineered strains. We show that a mathematical model built on a consensus picture of this control system is largely successful in explaining the phenotypes of mutants described so far. A few inconsistencies between the model and experiments indicate aspects of the mechanism that require revision. In addition, the model allows one to frame and critique hypotheses about how the division cycle is regulated in wild-type and mutant cells, to predict the phenotypes of new mutant combinations, and to estimate the effective values of biochemical rate constants that are difficult to measure directly in vivo. The model reproduces the time profiles of the different species in Figure 2 of the paper. The figure depicts the cycle of a daughter cell. Since the Mass Doubling Time (MDT) is 90 minutes, time t=90 from the model simulation will correspond to time t=0 in the paper. The model was successfully tested using MathSBML and SBML odeSolver. To create a valid SBML file, a local parameter k=1 was added in the reaction 'Inactivation_274_CDC20'. Also, in order to annotate the protein and to have the interaction in the reaction graph to match figure 1 of the article, the reaction rate constants k_{mad2}, k_{bub2} and k_{lte1} are considered as species and renamed as MAD2, BUB2 and LTE1 in the model. This model is hosted on BioModels Database and identified by: BIOMD0000000056 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

SUBMITTER: Nicolas Le Novère   

PROVIDER: BIOMD0000000056 | BioModels Database | 2006-05-08

REPOSITORIES: BioModels

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Integrative analysis of cell cycle control in budding yeast.

Chen Katherine C KC   Calzone Laurence L   Csikasz-Nagy Attila A   Cross Frederick R FR   Novak Bela B   Tyson John J JJ  

Molecular biology of the cell 20040528 8


The adaptive responses of a living cell to internal and external signals are controlled by networks of proteins whose interactions are so complex that the functional integration of the network cannot be comprehended by intuitive reasoning alone. Mathematical modeling, based on biochemical rate equations, provides a rigorous and reliable tool for unraveling the complexities of molecular regulatory networks. The budding yeast cell cycle is a challenging test case for this approach, because the con  ...[more]

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