Short answers, pulled from the story.
CLOCK is a gene encoding a basic helix-loop-helix-PAS transcription factor that affects both the persistence and period of circadian rhythms. It acts as an activator of downstream elements in the pathway that generates circadian rhythms. Its name is a backronym for circadian locomotor output cycles kaput.
The CLOCK gene was first identified in 1997 by Joseph Takahashi and his colleagues. They used forward mutagenesis screening of mice treated with N-ethyl-N-nitrosourea to create and identify mutations affecting circadian activity. The mutant mice displayed an abnormally long period of daily activity that proved heritable.
CLOCK dimerizes with a partner protein, CYCLE in flies or BMAL1 in mice, and binds E-box elements to switch on genes such as period, timeless, and cryptochrome. The proteins those genes make accumulate and form complexes that block CLOCK, shutting the genes off. Cycles of phosphorylation and degradation then restart the loop, creating the daily rhythm.
In flies, the dominant Jrk mutation lengthens the period to 24.8 hours in half of heterozygotes and makes the rest arrhythmic, while homozygotes lose rhythm entirely. In mice, the dominant-negative ClockΔ19 mutation lengthens periods in heterozygotes and causes arrhythmicity in homozygotes. Surprisingly, Clock-null mice with the gene fully knocked out display completely normal circadian rhythms.
The 3111C variant of CLOCK is associated with evening preference, increased insomnia, difficulty losing weight, and recurrence of major depressive episodes in bipolar disorder. Less methylation of the Clock promoter is linked to breast cancer, and 53 percent of microsatellite-instability colorectal cancers in one study carried somatic CLOCK mutations. Suppression of CLOCK may also correlate with obesity and type 2 diabetes.
The earliest circadian rhythms likely arose from light-driven cell-division cycles in ancestral prokaryotes, with the kaiA, kaiB, and kaiC gene clusters in cyanobacteria the oldest known clock genes. BMAL1 is paralogous to CLOCK, and their common ancestor probably predated the insect-vertebrate split roughly 500 million years ago. A 2004 review suggested CLOCK may have arisen from a duplication of the BMAL1 gene, though this remains speculative.