A model of yeast cell‐cycle regulation based on multisite phosphorylation
Abstract In order for the cell's genome to be passed intact from one generation to the next, the events of the cell cycle (DNA replication, mitosis, cell division) must be executed in the correct order, despite the considerable molecular noise inherent in any protein‐based regulatory system res...
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| Format: | Article |
| Language: | English |
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Springer Nature
2010-08-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2010.55 |
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| _version_ | 1850179751238434816 |
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| author | Debashis Barik William T Baumann Mark R Paul Bela Novak John J Tyson |
| author_facet | Debashis Barik William T Baumann Mark R Paul Bela Novak John J Tyson |
| author_sort | Debashis Barik |
| collection | DOAJ |
| description | Abstract In order for the cell's genome to be passed intact from one generation to the next, the events of the cell cycle (DNA replication, mitosis, cell division) must be executed in the correct order, despite the considerable molecular noise inherent in any protein‐based regulatory system residing in the small confines of a eukaryotic cell. To assess the effects of molecular fluctuations on cell‐cycle progression in budding yeast cells, we have constructed a new model of the regulation of Cln‐ and Clb‐dependent kinases, based on multisite phosphorylation of their target proteins and on positive and negative feedback loops involving the kinases themselves. To account for the significant role of noise in the transcription and translation steps of gene expression, the model includes mRNAs as well as proteins. The model equations are simulated deterministically and stochastically to reveal the bistable switching behavior on which proper cell‐cycle progression depends and to show that this behavior is robust to the level of molecular noise expected in yeast‐sized cells (∼50 fL volume). The model gives a quantitatively accurate account of the variability observed in the G1‐S transition in budding yeast, which is governed by an underlying sizer+timer control system. |
| format | Article |
| id | doaj-art-d97a2519af524bfba769f6d69a4b5945 |
| institution | OA Journals |
| issn | 1744-4292 |
| language | English |
| publishDate | 2010-08-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-d97a2519af524bfba769f6d69a4b59452025-08-20T02:18:25ZengSpringer NatureMolecular Systems Biology1744-42922010-08-016111810.1038/msb.2010.55A model of yeast cell‐cycle regulation based on multisite phosphorylationDebashis Barik0William T Baumann1Mark R Paul2Bela Novak3John J Tyson4Department of Biological Sciences, Virginia Polytechnic Institute and State UniversityDepartment of Electrical and Computer Engineering, Virginia Polytechnic Institute and State UniversityDepartment of Mechanical Engineering, Virginia Polytechnic Institute and State UniversityDepartment of Biochemistry, Centre for Integrative Systems BiologyDepartment of Biological Sciences, Virginia Polytechnic Institute and State UniversityAbstract In order for the cell's genome to be passed intact from one generation to the next, the events of the cell cycle (DNA replication, mitosis, cell division) must be executed in the correct order, despite the considerable molecular noise inherent in any protein‐based regulatory system residing in the small confines of a eukaryotic cell. To assess the effects of molecular fluctuations on cell‐cycle progression in budding yeast cells, we have constructed a new model of the regulation of Cln‐ and Clb‐dependent kinases, based on multisite phosphorylation of their target proteins and on positive and negative feedback loops involving the kinases themselves. To account for the significant role of noise in the transcription and translation steps of gene expression, the model includes mRNAs as well as proteins. The model equations are simulated deterministically and stochastically to reveal the bistable switching behavior on which proper cell‐cycle progression depends and to show that this behavior is robust to the level of molecular noise expected in yeast‐sized cells (∼50 fL volume). The model gives a quantitatively accurate account of the variability observed in the G1‐S transition in budding yeast, which is governed by an underlying sizer+timer control system.https://doi.org/10.1038/msb.2010.55bistabilitycell‐cycle variabilitysize controlstochastic modeltranscription–translation coupling |
| spellingShingle | Debashis Barik William T Baumann Mark R Paul Bela Novak John J Tyson A model of yeast cell‐cycle regulation based on multisite phosphorylation Molecular Systems Biology bistability cell‐cycle variability size control stochastic model transcription–translation coupling |
| title | A model of yeast cell‐cycle regulation based on multisite phosphorylation |
| title_full | A model of yeast cell‐cycle regulation based on multisite phosphorylation |
| title_fullStr | A model of yeast cell‐cycle regulation based on multisite phosphorylation |
| title_full_unstemmed | A model of yeast cell‐cycle regulation based on multisite phosphorylation |
| title_short | A model of yeast cell‐cycle regulation based on multisite phosphorylation |
| title_sort | model of yeast cell cycle regulation based on multisite phosphorylation |
| topic | bistability cell‐cycle variability size control stochastic model transcription–translation coupling |
| url | https://doi.org/10.1038/msb.2010.55 |
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