activating Clk. PER/TIM dimer accumulate in the early night and translocate in an orchestrated fashion into the nucleus several hours later, and binds to CLK/CYC dimers. Bound PER completely stops the transcriptional activity of CLK and CYC. In the early morning, the appearance of light causes PER and TIM proteins to breakdown in a network of transcriptional activation and repression. First, light activates the cry gene in the clock neurones. Although CRY is produced deep inside the brain, it is sensitive to UV and blue light, and thus it easily signals the brain cells the onset of light. It irreversibly and directly binds to TIM causing it to break down through proteosome-dependent ubiquitin-mediated degradation. The CRY's photolyase homology domain is used for light detection and phototransduction, whereas the carboxyl-terminal domain regulates CRY stability, CRY-TIM interaction, and circadian photosensitivity. The ubiquitination and subsequent degradation are aided by a different protein JET. Thus PER/TIM dimer dissociates, and the unbound PER becomes unstable. PER undergoes progressive phosphorylation and ultimately degradation. Absence of PER and TIM allows activation of clk and cyc genes. Thus, the clock is reset to commence the next circadian cycle. References Circadian rhythm circadian