Document Detail


A quantitative model of the effect of unreplicated DNA on cell cycle progression in frog egg extracts.
MedLine Citation:
PMID:  19490919     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jason Zwolak; Nassiba Adjerid; Elife Z Bagci; John J Tyson; Jill C Sible
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-05-31
Journal Detail:
Title:  Journal of theoretical biology     Volume:  260     ISSN:  1095-8541     ISO Abbreviation:  J. Theor. Biol.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-08-07     Completed Date:  2011-02-24     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  0376342     Medline TA:  J Theor Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  110-20     Citation Subset:  IM    
Affiliation:
Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, 24061, USA. jzwolak@vt.edu
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MeSH Terms
Descriptor/Qualifier:
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:
GM076112/GM/NIGMS NIH HHS; R01 GM076112-04/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
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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