Circadian Rhythms in Drosophila: A Connections Map

Russell N. Van Gelder^*

Department of Ophthalmology and Visual Sciences, Department of Molecular Biology and Pharmacology, Washington University Medical School, 660 South Euclid Avenue, St. Louis, MO 63110, USA.

Abstract: Genetic and biochemical experiments over the past decade have allowed the construction of a viable working model for the molecular mechanisms underlying circadian rhythm generation in Drosophila. The basic mechanism consists of two intertwined transcription-translation negative feedback loops. One loop--the "positive loop"--controls the rhythmic expression of a Per-Arnt-Sim (PAS)-domain-containing positive transcription factor, Clock. The second loop--the "negative loop"--controls the transcription of period and timeless, two genes encoding repressor proteins. The loops are intertwined because Period and Timeless directly repress transcription mediated by the Clock:Cycle heterodimer, whereas Clock:Cycle drives transcription of period and timeless, as well as that of vrille, a repressor of Clock expression. Other proteins, including kinases encoded by doubletime, shaggy, Andante, and Timekeeper, also have essential functions in the timekeeping mechanism. Light cycles can synchronize the Drosophila circadian pathway by directly stimulating Cryptochrome-dependent degradation of Timeless. This Pathway Map of the Drosophila circadian mechanism describes the individual known components of the fly circadian clock and their mutual interactions. An accompanying animation schematizes the dynamic interactions of the different components.

Science Viewpoint

R. N. Van Gelder, E. D. Herzog, W. J. Schwartz, P. H. Taghert, Circadian rhythms: In the loop at last. Science 300, 1534-1535 (2003). [Abstract] [Full Text]

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