Setting the Clock
by Christopher Hammond

Plants do it. Now we know humans do it, too.

For 120 years, scientists understood that a light-sensitive pigment in the retina allows humans to see. They also thought the same pigment sets your inner clock, which among other things keeps you from comfortably sleeping late after daylight-saving time.

Now Carolina researchers have found that another pigment, called cryptochrome, sets the clock in humans. Also known as circadian rhythms, the clock helps control the body's temperature, blood pressure, and mental activity.

This discovery could lead to a breakthrough for the winter blues and jet lag. People who suffer from a disease called seasonal affective disorder (SAD) become seriously depressed as days get shorter. Aziz Sancar, Kenan professor of biochemistry and biophysics at the School of Medicine, says it may be that SAD patients have a defective gene that fails to produce cryptochrome properly. Since it is linked to vitamin B-2, patients may simply suffer from a vitamin deficiency.

Plants offered the first clue.

"For twenty-five years—all of my career—I have worked on the enzyme, DNA photo-lyase, which uses visible light to repair ultraviolet DNA damage in bacteria," he says. "But we could not find photolyase in humans."

Meanwhile, other researchers found that cryptochrome, which regulates plant growth, was similar to plant photolyase. And scientists at the Human Genome Project found a human DNA sequence very similar to plant photolyase. "When I saw the results, it occurred to me that we had made an error," Sancar says.

Simply because Sancar had failed to find human photolyase activity did not mean the enzyme wasn't there. Maybe it did something else in humans.

Another clue came from blind mice whose inner clocks still responded to light-dark cycles. That would imply that something else in their eyes synchronizes their circadian rhythms to the sun.

In mice experiments, Sancar and Yasuhide Miyamoto, postdoctoral fellow in biochemistry, located cryptochrome. As they suspected, levels of the pigment had changed in parts of the brain that control circadian rhythms. Given the similarity in DNA sequences between mice and humans, their findings translate almost directly.

Sancar says the enzyme he had studied for years does more than simply repair DNA damage in bacteria. In humans, it controls the body's clock.

What's next? Sancar's work may provide a springboard for research into SAD, jet lag, and nighttime job performance. "It's not just a matter of understanding our proteins," Sancar says. "It has a great many practical applications."

This research appeared in the May 26th Proceedings of the National Academy of Sciences.