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Science

Internal clock mechanism found in enzyme present in all life

UK scientists have identified an enzyme that undergoes 24-hour chemical cycle, which may have larger implications for the broader study of the biochemical and physiological implications of sleep.

DNA graphic

Circadian rhythms may not rely as much on DNA as was believed

In a new study, British scientists have identified an enzyme present in all forms of life - ranging from humans down to the most basic algae - that regulates the circadian rhythm, or 24-hour internal clock.

In two papers to be published Thursday in the journal Nature, scientists from the University of Cambridge and the University of Edinburgh showed that this enzyme, called a peroxiredoxin, undergoes a 24-hour cycle of oxidation and reduction which may present a new step in understanding cyclical processes, like sleep.

Scientists say that the purpose of this molecule is to "clean up" peroxide, a byproduct of cellular functions, which can be harmful at elevated levels.

Previous theories of circadian rhythms suggested that the internal clock was regulated directly by DNA, but the new findings suggest that this may not be the case.

"Before, everyone understood that you needed this protein that was being made and the DNA in order to form a clock, and what we show is that all you need is that protein," explained Akhilesh Reddy, a professor of neuroscience at the University of Cambridge, and the lead author of the paper, in an interview with Deutsche Welle.

From human cells to algae

Algae

Scientists kept algae in total darkness for 24 hours, and found the same peroxiredoxin cycle

For the study, the researchers took purified red blood cells - which do not have DNA - from humans, monitored these enzymes and verified that they underwent this 24-hour chemical cycle.

Similarly, another team with scientists from Edinburgh, Cambridge, and Banyuls, France, found a similar day-long cycle in marine algae, even if the algae was kept in total darkness for 24 hours.

These two findings suggest that there is a process buried deep within all life, and can happen even in the absence of genetic material.

"Any organism has been exposed to a rhythmic environment," Reddy added. "It has a 24-hour cycle of light and dark. So, you can imagine that all throughout evolutionary history, there would have been a selective pressure to evolve a mechanism to keep track of this 24-hour day."

He pointed out that many single-celled organisms, for example, prefer to divide at night, as UV light that shines during the day damages their DNA.

Other scientists who study circadian rhythms said that this new approach was promising.

"These are very interesting papers because they point to a mechanism of circadian clocks, which is not based on gene regulation," said Albert Goldbeter, a professor of theoretical chronobiology at the Free University of Brussels, who was not part of the study.

Still, Goldbeter was quick to point out that this new research will add to the broader understanding of circadian rhythms, rather than completely altering accepted theory, adding that there "is probably crosstalk between the different mechanisms."

"I wouldn't say that this obliterates 20 years of work on clock gene regulation; it offers a complimentary view," he told Deutsche Welle.

New findings may ultimately help sleep research

Sleeping polar bear

By understanding peroxiredoxin, scientists hope to gain a broader understanding of how sleep works

Reddy added that with these new findings of peroxiredoxin, there may be new hope for people who suffer from sleep disorders, or people with neurodegenerative diseases that prevent them from sleeping properly.

"This peroxiredoxin is an enzyme, something that you can target with drugs,” he said. “They're quite druggable targets. You might be able to effectively change the circadian rhythm. People have been looking at it from the DNA aspect, not the enzyme.”

More broadly, he also suggested that this research may ultimately be able to help people who work shifts, and people who frequently suffer from jet lag.

Reddy noted that people who regularly work odd hours have been shown to be at a higher risk of strokes, heart diseases and other maladies.

"Actually we're working against our biology," he said. "We weren't actually built to have light on in the middle of the night."

Author: Cyrus Farivar
Editor: Nathan Witkop

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