NIH Press Release
NATIONAL INSTITUTES OF HEALTH
National Institute of General Medical Sciences
National Institute of Mental Health

EMBARGOED FOR RELEASE
Thursday, May 1, 1997
5:00 PM Eastern Time

Doris Brody, NIGMS
(301) 496-7301
Jules Asher, NIMH
(301) 443-4536

How Light- and Temperature-Responsive Molecules
Make the Biological Clock Run

Scientists studying circadian rhythms in the model organism Neurospora (a type of bread mold) have made key discoveries that help explain how the organismís biological clock is regulated both by light and by temperature. Understanding the molecular mechanisms of biological clocks may have important implications for human health because alterations in human biological clocks are linked to many conditions, including depression, seasonal affective disorder, sleep disorders, and jet lag. Dr. Jay Dunlap and his colleagues at Dartmouth Medical School in Hanover, NH, report their findings May 2 in two papers appearing in Cell and one in Science.

The Cell papers describe how the key Neurospora clock gene, called frq, gives rise to two forms of the FRQ protein that operate in a time-of-day-dependent manner, producing a feedback cycle that is the molecular basis of the Neurospora circadian clock. These proteins are regulated by temperature.

The Science paper shows that two other proteins (WC-1 and WC-2), which regulate light responses, can actually work in the dark and are required for the clock to function. Interestingly, Dr. Dunlap and colleague Dr. Jennifer Loros find both proteins to contain a particular amino acid sequence called the PAS domain that is conserved in the biological clocks of a number of distantly related species. The conservation of this sequence indicates that many, and possibly all, biological clocks may share common molecular components.

This work was supported by the National Institute of General Medical Sciences (NIGMS), a component of the National Institutes of Health that supports basic biomedical research; by another NIH component, the National Institute of Mental Health (NIMH); and also by the National Science Foundation and the United States Air Force.


Resources:

Crosthwaite SK et al. Neurospora wc-1 and wc-2: Transcription, Photoresponses, and the Origins of Circadian Rhythmicity. Science 1997;276:763-9.

Garceau NY et al. Alternative Initiation of Translation and Time-Specific Phosphorylation Yield Multiple Forms of the Essential Clock Protein FREQUENCY. Cell 1997;89:469-76.

Liu Y et al. Thermally Regulated Translational Control of FRQ Mediates Aspects of Temperature Responses in the Neurospora Circadian Clock. Ibid., p. 477-86.

Dr. Jay Dunlap
Department of Biochemistry
Dartmouth Medical School
(603) 650-1616
For scientific perspective on the papers
Call the NIGMS Public Information Office
at (301) 496-7301 to interview
Dr. Michael Sesma,
Program Director,Division of Genetics
and Developmental Biology, NIGMS