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The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo.

The Period2 gene plays a key role in controlling circadian rhythm in mice. We report here that mice deficient in the mPer2 gene are cancer prone. After gamma radiation, these mice show a marked increase in tumor development and reduced apoptosis in thymocytes. The core circadian genes are induced by gamma radiation in wild-type mice but not in mPer2 mutant mice. Temporal expression of genes involved in cell cycle regulation and tumor suppression, such as Cyclin D1, Cyclin A, Mdm-2, and Gadd45alpha, is deregulated in mPer2 mutant mice. In particular, the transcription of c-myc is controlled directly by circadian regulators and is deregulated in the mPer2 mutant. Our studies suggest that the mPer2 gene functions in tumor suppression by regulating DNA damage-responsive pathways.

Pubmed ID: 12372299


  • Fu L
  • Pelicano H
  • Liu J
  • Huang P
  • Lee C



Publication Data

October 4, 2002

Associated Grants


Mesh Terms

  • ARNTL Transcription Factors
  • Animals
  • Apoptosis
  • Basic Helix-Loop-Helix Transcription Factors
  • Blotting, Northern
  • Blotting, Western
  • Cell Cycle
  • Cell Cycle Proteins
  • Cell Division
  • Cyclin A
  • Cyclin D1
  • DNA Damage
  • Dimerization
  • Flow Cytometry
  • Gamma Rays
  • Genetic Predisposition to Disease
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Neoplasms, Experimental
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Period Circadian Proteins
  • Phenotype
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-mdm2
  • Proto-Oncogene Proteins c-myc
  • Thymus Gland
  • Time Factors
  • Transcription Factors
  • Transfection
  • Tumor Suppressor Protein p53