How genes control 24-hour circadian rhythm in humans

Researchers have discovered how genes keep the circadian clocks in all human cells in time and in proper rhythm with the 24-hour day, as well as the seasons.
The finding has implications for the development of drugs for various diseases such as cancers and diabetes, as well as conditions such as metabolic syndrome, insomnia, seasonal affective disorder, obesity, and even jetlag.
"Discovering how these circadian clock genes interact has been a long-time coming," said Aziz Sancar, Professor at the University of North Carolina Health Care (UNC) School of Medicine and senior author.
"We've known for a while that four proteins were involved in generating daily rhythmicity but not exactly what they did. Now we know how the clock is reset in all cells. So we have a better idea of what to expect if we target these proteins with therapeutics," said Sancar.

In all human cells, there are four genes - Cryptochrome, Period, CLOCK, and BMAL1 - that work in unison to control the cyclical changes in human physiology, such as blood pressure, body temperature, and rest-sleep cycles.
The way in which these genes control physiology helps prepare us for the day. This is called the circadian clock. It keeps us in proper physiological rhythm.

When we try to fast-forward or rewind the natural 24-hour day, such as when we fly seven time zones away, our circadian clocks don't let us off easy; the genes and proteins need time to adjust.
Jetlag is the feeling of our cells "realigning" to their new environment and the new starting point of a solar day.

CLOCK and BMAL1 bind to a pair of genes called Period and Cryptochrome and turn them on to express proteins, which - after several modifications - wind up suppressing CLOCK and BMAL1 activity. Then, the Period and Cryptochrome proteins are degraded, allowing for the circadian clock to begin again.
"It's a feedback loop. The inhibition takes 24 hours. This is why we can see gene activity go up and then down throughout the day," said Sancar, who discovered Cryptochrome in 1998.
But scientists didn't know exactly how that gene suppression and protein degradation happened at the back end.
The study was published in the journal Genes and Development.