Entrainment of the mammalian cell cycle by the circadian clock: modeling two coupled cellular rhythms.

The cell division cycle and the circadian clock represent two major cellular rhythms. These two periodic processes are coupled in multiple ways, given that several molecular components of the cell cycle network are controlled in a circadian manner. For example, in the network of cyclin-dependent kin...

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Autores principales:	Claude Gérard, Albert Goldbeter
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/61edf0864a0845e98351e37e3a24c718
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spelling	oai:doaj.org-article:61edf0864a0845e98351e37e3a24c7182021-11-18T05:51:18ZEntrainment of the mammalian cell cycle by the circadian clock: modeling two coupled cellular rhythms.1553-734X1553-735810.1371/journal.pcbi.1002516https://doaj.org/article/61edf0864a0845e98351e37e3a24c7182012-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22693436/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The cell division cycle and the circadian clock represent two major cellular rhythms. These two periodic processes are coupled in multiple ways, given that several molecular components of the cell cycle network are controlled in a circadian manner. For example, in the network of cyclin-dependent kinases (Cdks) that governs progression along the successive phases of the cell cycle, the synthesis of the kinase Wee1, which inhibits the G2/M transition, is enhanced by the complex CLOCK-BMAL1 that plays a central role in the circadian clock network. Another component of the latter network, REV-ERBα, inhibits the synthesis of the Cdk inhibitor p21. Moreover, the synthesis of the oncogene c-Myc, which promotes G1 cyclin synthesis, is repressed by CLOCK-BMAL1. Using detailed computational models for the two networks we investigate the conditions in which the mammalian cell cycle can be entrained by the circadian clock. We show that the cell cycle can be brought to oscillate at a period of 24 h or 48 h when its autonomous period prior to coupling is in an appropriate range. The model indicates that the combination of multiple modes of coupling does not necessarily facilitate entrainment of the cell cycle by the circadian clock. Entrainment can also occur as a result of circadian variations in the level of a growth factor controlling entry into G1. Outside the range of entrainment, the coupling to the circadian clock may lead to disconnected oscillations in the cell cycle and the circadian system, or to complex oscillatory dynamics of the cell cycle in the form of endoreplication, complex periodic oscillations or chaos. The model predicts that the transition from entrainment to 24 h or 48 h might occur when the strength of coupling to the circadian clock or the level of growth factor decrease below critical values.Claude GérardAlbert GoldbeterPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 5, p e1002516 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Claude Gérard Albert Goldbeter Entrainment of the mammalian cell cycle by the circadian clock: modeling two coupled cellular rhythms.
description	The cell division cycle and the circadian clock represent two major cellular rhythms. These two periodic processes are coupled in multiple ways, given that several molecular components of the cell cycle network are controlled in a circadian manner. For example, in the network of cyclin-dependent kinases (Cdks) that governs progression along the successive phases of the cell cycle, the synthesis of the kinase Wee1, which inhibits the G2/M transition, is enhanced by the complex CLOCK-BMAL1 that plays a central role in the circadian clock network. Another component of the latter network, REV-ERBα, inhibits the synthesis of the Cdk inhibitor p21. Moreover, the synthesis of the oncogene c-Myc, which promotes G1 cyclin synthesis, is repressed by CLOCK-BMAL1. Using detailed computational models for the two networks we investigate the conditions in which the mammalian cell cycle can be entrained by the circadian clock. We show that the cell cycle can be brought to oscillate at a period of 24 h or 48 h when its autonomous period prior to coupling is in an appropriate range. The model indicates that the combination of multiple modes of coupling does not necessarily facilitate entrainment of the cell cycle by the circadian clock. Entrainment can also occur as a result of circadian variations in the level of a growth factor controlling entry into G1. Outside the range of entrainment, the coupling to the circadian clock may lead to disconnected oscillations in the cell cycle and the circadian system, or to complex oscillatory dynamics of the cell cycle in the form of endoreplication, complex periodic oscillations or chaos. The model predicts that the transition from entrainment to 24 h or 48 h might occur when the strength of coupling to the circadian clock or the level of growth factor decrease below critical values.
format	article
author	Claude Gérard Albert Goldbeter
author_facet	Claude Gérard Albert Goldbeter
author_sort	Claude Gérard
title	Entrainment of the mammalian cell cycle by the circadian clock: modeling two coupled cellular rhythms.
title_short	Entrainment of the mammalian cell cycle by the circadian clock: modeling two coupled cellular rhythms.
title_full	Entrainment of the mammalian cell cycle by the circadian clock: modeling two coupled cellular rhythms.
title_fullStr	Entrainment of the mammalian cell cycle by the circadian clock: modeling two coupled cellular rhythms.
title_full_unstemmed	Entrainment of the mammalian cell cycle by the circadian clock: modeling two coupled cellular rhythms.
title_sort	entrainment of the mammalian cell cycle by the circadian clock: modeling two coupled cellular rhythms.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/61edf0864a0845e98351e37e3a24c718
work_keys_str_mv	AT claudegerard entrainmentofthemammaliancellcyclebythecircadianclockmodelingtwocoupledcellularrhythms AT albertgoldbeter entrainmentofthemammaliancellcyclebythecircadianclockmodelingtwocoupledcellularrhythms
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Entrainment of the mammalian cell cycle by the circadian clock: modeling two coupled cellular rhythms.

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