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Published Online August 21, 2003
Science DOI: 10.1126/science.1086271

Research Articles

Submitted on April 29, 2003
Accepted on August 8, 2003

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

Takuya Matsuo 1, Shun Yamaguchi 2, Shigeru Mitsui 2, Aki Emi 2, Fukuko Shimoda 2, Hitoshi Okamura 2*

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

* To whom correspondence should be addressed. E-mail: okamurah{at}kobe-u.ac.jp.

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.


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