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

Release Date:
5/1/1997
Contact:
Doris Brody, NIGMS
(301) 496-7301

Scientists studying circadian rhythms in the model organism Neurospora (a type of bread mold) have made key discoveries that help explain how the organism's 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, a component of the National Institutes of Health that supports basic biomedical research; by another NIH component, the National Institute of Mental Health; 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 (603) 650-1616
Department of Biochemistry
Dartmouth Medical School

For scientific perspectives contact the NIGMS Office of Communications and Public Liaison at (301) 496-7301