| Computational analysis of mammalian cell division gated by a circadian clock: quantized cell cycles and cell size control. | |
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MedLine Citation:
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PMID: 18057329 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cell cycle and circadian rhythms are conserved from cyanobacteria to humans with robust cyclic features. Recently, molecular links between these two cyclic processes have been discovered. Core clock transcription factors, Bmal1 and Clock (Clk), directly regulate Wee1 kinase, which inhibits entry into the mitosis. We investigate the effect of this connection on the timing of mammalian cell cycle processes with computational modeling tools. We connect a minimal model of circadian rhythms, which consists of transcription-translation feedback loops, with a modified mammalian cell cycle model from Novak and Tyson (2004). As we vary the mass doubling time (MDT) of the cell cycle, stochastic simulations reveal quantized cell cycles when the activity of Wee1 is influenced by clock components. The quantized cell cycles disappear in the absence of coupling or when the strength of this link is reduced. More intriguingly, our simulations indicate that the circadian clock triggers critical size control in the mammalian cell cycle. A periodic brake on the cell cycle progress via Wee1 enforces size control when the MDT is quite different from the circadian period. No size control is observed in the absence of coupling. The issue of size control in the mammalian system is debatable, whereas it is well established in yeast. It is possible that the size control is more readily observed in cell lines that contain circadian rhythms, since not all cell types have a circadian clock. This would be analogous to an ultradian clock intertwined with quantized cell cycles (and possibly cell size control) in yeast. We present the first coupled model between the mammalian cell cycle and circadian rhythms that reveals quantized cell cycles and cell size control influenced by the clock. |
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Authors:
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Judit Zámborszky; Christian I Hong; Attila Csikász Nagy |
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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 |
Journal Detail:
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Title: Journal of biological rhythms Volume: 22 ISSN: 0748-7304 ISO Abbreviation: J. Biol. Rhythms Publication Date: 2007 Dec |
Date Detail:
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Created Date: 2007-12-06 Completed Date: 2008-01-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8700115 Medline TA: J Biol Rhythms Country: United States |
Other Details:
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Languages: eng Pagination: 542-53 Citation Subset: IM |
Affiliation:
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Materials Structure and Modeling Research Group of the Hungarian Academy of Sciences and Department of Applied Biotechnology and Food Science, Budapest University of Technology and Economics, Budapest, Hungary. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Cycle / physiology* Cell Division / physiology* Cell Size* Circadian Rhythm / physiology* Kinetics Mammals Models, Biological Periodicity |
| Grant Support | |
ID/Acronym/Agency:
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GM34985/GM/NIGMS NIH HHS; MH44651/MH/NIMH NIH HHS |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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