Sixteen years after scientists found the genes that control the circadian clock in all cells, U.S. researchers have now discovered how genes keep the circadian clocks in all human cells in time and in proper rhythm within the 24-hour period.
A circadian rhythm is any biological process that displays an oscillation of about 24 hours.
They found that two genes — Period and Cryptochrome — have complementary roles.
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 jet lag.
“We have 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,” explained Aziz Sancar, professor of biochemistry and biophysics at the University of North Carolina’s school of medicine.
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.
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 is 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.
The paper was published in the journal Genes and Development .
