Figure 1.

The circadian clock machinery. Twenty-four hour rhythms are generated by a cell-autonomous and autoregulatory transcriptional-translational feedback loop. In its simplest form, the core circadian protein, CLOCK, forms a complex with brain and muscle ARNT-like protein 1 (BMAL1). This complex binds to enhancer box (E-box) regulatory element and activates transcription of the Period (Per) and Cryptochrome (Cry) genes. As PERs and CRYs accumulate during the day, they dimerize and translocate back to the nucleus where they interact with CLOCK and BMAL1 to repress their own transcription. As these negative elements are degraded by casein kinases (CK) at night, repression of CLOCK and BMAL1 is removed, and a new cycle of transcription begins the following morning. The CLOCK-BMAL1 complex also binds to an array of clock-controlled genes (ccg) that ultimately regulate biological processes such as sleep-wake cycles, body temperature, hormone secretion, feeding, and activity.