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 RIS Download
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