Figure 1.

Circadian oscillations result from the transcription, translation, accumulation, and degradation of genes. This simplified schematic depicts the feedback mechanism of the canonical clock genes that results in circadian oscillation. The proteins BMAL1 and CLOCK dimerize and bind DNA at E-box binding sites, resulting in transcription of genes under the control of these binding elements. These genes include Per1 and Per2, Cry1 and Cry2, and other genes involved in circadian behavioral and physiological responses. The Per and Cry genes accumulate in the cytoplasm where they dimerize and are then transported back to the nucleus. The Per-Cry dimer inhibits binding of BMAL1 and CLOCK to DNA, repressing transcription of downstream genes. In this way, the accumulation of Per and Cry repress their own expression, establishing a system that oscillates based on the expression, accumulation, and subsequent repression of these genes.