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Science 302 (5643): 255-259

Copyright © 2003 by the American Association for the Advancement of Science

Control Mechanism of the Circadian Clock for Timing of Cell Division in Vivo

Takuya Matsuo,1,2* Shun Yamaguchi,1* Shigeru Mitsui,1 Aki Emi,1 Fukuko Shimoda,1 Hitoshi Okamura1{dagger}

Abstract: Cell division in many mammalian tissues is associated with specific times of day, but just how the circadian clock controls this timing has not been clear. Here, we show in the regenerating liver (of mice) that the circadian clock controls the expression of cell cycle–related genes that in turn modulate the expression of active Cyclin B1-Cdc2 kinase, a key regulator of mitosis. Among these genes, expression of wee1 was directly regulated by the molecular components of the circadian clockwork. In contrast, the circadian clockwork oscillated independently of the cell cycle in single cells. Thus, the intracellular circadian clockwork can control the cell-division cycle directly and unidirectionally in proliferating cells.

1 Division of Molecular Brain Science, Department of Brain Sciences, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650–0017, Japan.
2 Department of Physics, Informatics and Biology, Yamaguchi University, Yamaguchi 753–8512, Japan.

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: okamurah{at}

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Am J Physiol Regulatory Integrative Comp Physiol 292, R160-R166
   Abstract »    Full Text »    PDF »
Properties, Entrainment, and Physiological Functions of Mammalian Peripheral Oscillators.
M. Stratmann and U. Schibler (2006)
J Biol Rhythms 21, 494-506
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Improved Tumor Control through Circadian Clock Induction by Seliciclib, a Cyclin-Dependent Kinase Inhibitor..
I. Iurisci, E. Filipski, J. Reinhardt, S. Bach, A. Gianella-Borradori, S. Iacobelli, L. Meijer, and F. Levi (2006)
Cancer Res. 66, 10720-10728
   Abstract »    Full Text »    PDF »
The Neurospora Checkpoint Kinase 2: A Regulatory Link Between the Circadian and Cell Cycles.
A. M. Pregueiro, Q. Liu, C. L. Baker, J. C. Dunlap, and J. J. Loros (2006)
Science 313, 644-649
   Abstract »    Full Text »    PDF »

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