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

American Association for the Advancement of Science (AAAS) - Tập 302 Số 5643 - Trang 255-259 - 2003
Takuya Matsuo1,2, Shun Yamaguchi1,2, Shigeru Mitsui1,2, Aki Emi1,2, Fukuko Shimoda1,2, Hitoshi Okamura1,2
1Department of Physics, Informatics and Biology, Yamaguchi University, Yamaguchi 753–8512, Japan.
2Division of Molecular Brain Science, Department of Brain Sciences, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650–0017, Japan.

Tóm tắt

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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The authors wish to thank M. Iwai (Kyoto Prefectural University of Medicine) for advising the technique of hepatectomy G. T. J. van der Horst (Erasmus University) for providing access to Cry -deficient mice and A. Ishida and T. Okamoto (Kobe University) for technical assistance. Supported in part by grants from the Special Coordination Funds; the Grant-in-Aid for the Scientific Research on Priority Areas of the Ministry of Education Culture Sports Science and Technology of Japan; the Kanae Foundation for Life and Sociomedical Science; and the Inamori Foundation.