Control mechanism of the circadian clock for timing of cell division in vivo

Science. 2003 Oct 10;302(5643):255-9. doi: 10.1126/science.1086271. Epub 2003 Aug 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Biological Clocks*
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism*
  • CLOCK Proteins
  • Cell Cycle
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Division*
  • Circadian Rhythm*
  • Cryptochromes
  • Cyclin B / genetics
  • Cyclin B / metabolism*
  • Cyclin B1
  • Drosophila Proteins*
  • Eye Proteins*
  • Flavoproteins / genetics
  • Flavoproteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Hepatectomy
  • Hepatocytes / cytology*
  • Hepatocytes / metabolism
  • Kinetics
  • Liver Regeneration
  • Mice
  • Mice, Inbred C57BL
  • Mitosis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Period Circadian Proteins
  • Phosphorylation
  • Photoreceptor Cells, Invertebrate*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Receptors, G-Protein-Coupled
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic

Substances

  • ARNTL Transcription Factors
  • Bmal1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Ccnb1 protein, mouse
  • Cell Cycle Proteins
  • Cryptochromes
  • CycB protein, Drosophila
  • Cyclin B
  • Cyclin B1
  • Drosophila Proteins
  • Eye Proteins
  • Flavoproteins
  • Nuclear Proteins
  • Per1 protein, mouse
  • Per2 protein, mouse
  • Period Circadian Proteins
  • Receptors, G-Protein-Coupled
  • Trans-Activators
  • Transcription Factors
  • cry protein, Drosophila
  • CLOCK Proteins
  • Clock protein, mouse
  • Protein-Tyrosine Kinases
  • Wee1 protein, mouse
  • CDC2 Protein Kinase