RAS signaling of circadian output

Jun 17 2007

In the June 15th issue of G&D, Drs. Jay Dunlap and Jennifer Loros, with colleagues at Dartmouth Medical School, have finally cloned the band gene, and have found that it is an allele of ras-1.

This finding posits RAS signaling as a key mediator of circadian output.

The fungus Neurospora crassa is one of the best studied laboratory systems for circadian rhythms. However, over the past 50 years, almost all of the work done on Neurospora has used laboratory strains carrying the band mutation, because it enables researchers to visualize the fungus' daily circadian growth cycles. Research on Neurospora using this strain has contributed to understanding the basis of jet lag as well as some affective disorders.

While the band mutation has facilitated Neurospora clock observation, researchers are only now realizing what protein is encoded by the band gene, and how the subtle nature of the disruption in the band gene affects Neurospora circadian rhythms.

The Dartmouth team demonstrate that the band mutation is a dominant point mutation in ras-1 that causes a slight increase in GTP exchange, and therefore slightly higher activity levels. Says Dunlap, "Understanding the molecular nature of band makes us all look at output from the circadian clock in a different and clearer way. It's been a long time coming."