Rhythmic levels of PER protein play a key role in the circadian clock's feedback control

Constitutive expression of PER2 in the brain and SCN of transgenic mice caused a complete loss of behavioral circadian rhythms.

• Circadian rhythms in mammals are influenced by a transcriptional negative feedback loop involving PER and CRY proteins.
• Current models suggest that CRY is the main repressor of this feedback loop, while PER has a secondary role.
• However, disrupting the clock in fibroblasts and liver was primarily linked to the expression of PER, not CRY1.
• Rhythmic levels of PER2 are shown to be essential for maintaining circadian oscillations in both cells and living organisms.
• Biochemical evidence indicates that PER2 directly and rhythmically binds to the CLOCK:BMAL1 complex, while CRY interacts indirectly.

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