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Clockwork Clues Determined

he cellular timekeepers.

The work is supported by the National Institutes of Health (National Institute of General Medical Sciences and the National Institute of Mental Health), the National Science Foundation, and in part by the U.S. Air Force.

Loros and Dunlap have studied the clock signals that tell bread mold when to send out spores, delineating how the clock is assembled and how light resets the biological clock. Watershed studies on the Neurospora clock mechanisms have predicted and presaged subsequent work in mammals by several years, Dunlap noted. What is true for the Neurospora clock has been true in mice and will probably be true in people.

The current work expands investigations of the intricate feedback loop that determines how the circadian clocks operate. The loop relies on levels of the FRQ clock protein that feeds back to shut off activity of the gene that produces it. Visible light and high ambient temperatures, interpreted as dusk (going from light to dark) trigger a delay that lengthens the circadian cycle; low temperature and darkness, read as dawn, drive the clock rhythms in the opposite direction, advancing the clock and shortening the cycle.

To determine the relative strength of the two factors, the investigators forced light and temperature to compete with each other in conditions of cool light and warm darkness. They measured the levels and ratios of the FRQ protein and its related gene components and discovered that contrary to previous assumptions, temperature was more effective than light in triggering the clock rhythms.

Moreover, the relation among the clock components, not the absolute amounts, set the new internal time.

Given the parallels between the bread mold and mammalian systems, the findings have implications for humans, the researchers note. They suggest that in the human brain, a low point for key timekeeper proteins could be just before dawn, corresponding to the temperature nadir for healt
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Contact: Hali Wickner
Hali.Wickner@Dartmouth.Edu
603-650-1520
Dartmouth Medical School
6-Aug-1998


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