| A quantitative model of the effect of unreplicated DNA on cell cycle progression in frog egg extracts. | |
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MedLine Citation:
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PMID: 19490919 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A critical goal in cell biology is to develop a systems-level perspective of eukaryotic cell cycle controls. Among these controls, a complex signaling network (called 'checkpoints') arrests progression through the cell cycle when there is a threat to genomic integrity such as unreplicated or damaged DNA. Understanding the regulatory principles of cell cycle checkpoints is important because loss of checkpoint regulation may be a requisite step on the roadway to cancer. Mathematical modeling has proved to be a useful guide to cell cycle regulation by revealing the importance of bistability, hysteresis and time lags in governing cell cycle transitions and checkpoint mechanisms. In this report, we propose a mathematical model of the frog egg cell cycle including effects of unreplicated DNA on progression into mitosis. By a stepwise approach utilizing parameter estimation tools, we build a model that is grounded in fundamental behaviors of the cell cycle engine (hysteresis and time lags), includes new elements in the signaling network (Myt1 and Chk1 kinases), and fits a large and diverse body of data from the experimental literature. The model provides a validated framework upon which to build additional aspects of the cell cycle checkpoint signaling network, including those control signals in the mammalian cell cycle that are commonly mutated in cancer. |
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Authors:
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Jason Zwolak; Nassiba Adjerid; Elife Z Bagci; John J Tyson; Jill C Sible |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-05-31 |
Journal Detail:
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Title: Journal of theoretical biology Volume: 260 ISSN: 1095-8541 ISO Abbreviation: J. Theor. Biol. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-08-07 Completed Date: 2011-02-24 Revised Date: 2011-11-02 |
Medline Journal Info:
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Nlm Unique ID: 0376342 Medline TA: J Theor Biol Country: England |
Other Details:
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Languages: eng Pagination: 110-20 Citation Subset: IM |
Affiliation:
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Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, 24061, USA. jzwolak@vt.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Cycle / genetics* DNA Replication / genetics* DNA-Binding Proteins / physiology Mitosis / genetics Models, Genetic* Ovum / cytology Protein Kinases / physiology Signal Transduction / genetics Transcription Factors / physiology Xenopus Proteins / physiology Xenopus laevis / genetics |
| Grant Support | |
ID/Acronym/Agency:
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GM076112/GM/NIGMS NIH HHS; R01 GM076112-04/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; 0/Myt1 protein, Xenopus; 0/Transcription Factors; 0/Xenopus Proteins; EC 2.7.-/Protein Kinases; EC 2.7.11.1/Checkpoint kinase 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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