How PER Protein Controls the Fruit Fly's Body Clock Both on and off DNA

In the Drosophila model, the circadian repressor PERIOD (PER) exhibits two mechanisms to inhibit CLOCK/CYCLE (CLK/CYC)-mediated transcription.

• PER is recruited to circadian promoters, leading to a decrease in CLK/CYC activity at night.
• The reduction in CLK/CYC activity is proportional to the amount of PER bound to DNA.
• CLK is released from DNA and forms a strong off-DNA complex with PER in a roughly 1:1 ratio.
• Dynamic changes in PER levels bound to CLK are crucial for transcriptional repression.
• These mechanisms may involve processes that occur before post-translational events and could also apply to mammals.

Simplified