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 7 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 wildtype 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.