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Genes may help reset circadian clock.

Researchers know from past experiments that morning light calibrates the biological clock in the brain to keep it running on a 24-hour schedule. But scientists have only a dim understanding of how this process works. Now a group of researchers suggests that two light-sensitive genes tell a cockeyed clock to reset itself.

The biological clock -- a group of nerve cells clustered in the hypothalamus, at the base of the brain -- regulates daily cycles such as sleepiness, hormone levels and body temperature in mammals.

In the new study, Joseph S. Takahashi and his co-workers at Northwestern University in Evanston, Ill., kept hamsters in complete darkness for seven days and then exposed them to a brief, predawn light burst. The flash activated a gene called jun-B in the brain, they report in the March 20 SCIENCE. In 1990, Takahashi's group discovered that a gene called c-fos responded similarly to light.

The researchers now believe that these two genes work in concert to stimulate the production of a protein called AP-1 transcription factor, which may spark other genes within the brain to reset the biological clock.

"There is an extremely tight correlation between the effects of light on the clock and its resetting, and the effects of light on the genes and AP-1," Takahashi says.

Although c-fos and jun-B serve many different purposes in cells throughout the brain, they appear to have a specific role in the resetting process, he says. "When you expose these animals to light, c-fos and jun-B don't change in any other part of the brain," he explains. "They only change in that one place [the circadian clock]."

Interestingly, the circadian clock appears to control when c-fos and jun-B will respond. "The clock only allowed the gene to go on in the nighttime, not in the daytime," Takahashi says.

The new findings represent an important step toward a better understanding of the resetting mechanism, although many mysteries remain. "AP-1 is just half of the story," says neurobiologist Stephen P. Hunt of the University of Cambridge Medical School in England. Hunt speculates that many proteins like AP-1 may help reset the clock. "It's going to be enormously complicated to work out," he says.
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Author:Stroh, Michael
Publication:Science News
Article Type:Brief Article
Date:Mar 28, 1992
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