The circadian gene per1 plays an important role in cell growth and DNA damage control in human cancer cells

Mol Cell. 2006 May 5;22(3):375-82. doi: 10.1016/j.molcel.2006.03.038.


The Per1 gene is a core clock factor that plays an essential role in generating circadian rhythms. Recent data reveal that major biological pathways, including those critical to cell division, are under circadian control. We report here that Per1 provides an important link between the circadian system and the cell cycle system. Overexpression of Per1 sensitized human cancer cells to DNA damage-induced apoptosis; in contrast, inhibition of Per1 in similarly treated cells blunted apoptosis. The apoptotic phenotype was associated with altered expression of key cell cycle regulators. In addition, Per1 interacted with the checkpoint proteins ATM and Chk2. Ectopic expression of Per1 in human cancer cell lines led to significant growth reduction. Finally, Per1 levels were reduced in human cancer patient samples. Our results highlight the importance of circadian regulation to fundamental cellular functions and support the hypothesis that disruption of core clock genes may lead to cancer development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / radiation effects
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Circadian Rhythm / genetics*
  • Cyclin-Dependent Kinase Inhibitor p21 / antagonists & inhibitors
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cyclins / genetics
  • Cyclins / metabolism
  • DNA Damage / genetics*
  • Down-Regulation / genetics
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / pathology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Period Circadian Proteins
  • Protein Binding
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Radiation, Ionizing
  • Tumor Cells, Cultured
  • Up-Regulation / genetics


  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Nuclear Proteins
  • PER1 protein, human
  • Period Circadian Proteins
  • RNA, Messenger
  • Protein-Tyrosine Kinases
  • WEE1 protein, human
  • CDC2 Protein Kinase