The Period (Per) genes are key circadian rhythm regulators in mammals. 
Expression of the mouse Per (mPer) genes have diurnal pattern in the 
suprachiamstic nuclei and in peripheral tissues. Genetic ablation mPER1 and 
mPER2 function results in a complete loss of circadian rhythm control based on 
wheel running activity in mice. In addition, these animals also display apparent 
premature aging and significant increase in neoplastic and hyperplastic 
phenotypes. When challenged by gamma-radiation, mPer2 deficient mice response by 
rapid hair graying, are deficient in p53-mediated apoptosis in thymocytes and 
have robust tumor occurrences. Our studies have demonstrated that the circadian 
clock function is very important for cell cycle, DNA damage response and tumor 
suppression in vivo. Temporal expression of genes involved in cell cycle 
regulation and tumor suppression, such as c-Myc, Cyclin D1, Cyclin A, Mdm-2 and 
Gadd45alpha is deregulated in mPer2 mutant mice. In addition, genetic studies 
have demonstrated that many key regulators of cell cycle and growth control are 
also important circadian clock regulators confirming the critical role of 
circadian function in organismal homeostasis. Recently studies of human breast 
and endometrial cancers revealed that the loss and deregulation of PERIOD 
proteins is common in the tumor cells.