The circadian clock is maintained by well-defined, daily fluctuations in the Period and Timeless proteins that negatively regulate the transcription of their own genes. In the November 14 Nature, Brigitte Grima and colleagues describe the mechanism responsible for the phosphorylation-dependent control of Period and Timeless protein degradation in the Drosophila clock (Nature, 420:178-182, November 14, 2002).

Investigation of components of the SCF-mediated ubiquitin proteosome pathway led to the identification of the Slimb protein as an essential cog in the fly brain clock. The Drosophila Slimb gene (Slmb) encodes an F-box/WD40 protein that regulates the levels of different transcription factors. Rescuing the developmental lethality associated with Slmb mutation revealed that adult Slmb mutants were completely arrhythmic under constant darkness (DD) conditions. In DD conditions Period and Timeless oscillations were abolished in the Slmb mutants and hyperphosphorylated Period accumulated.

This is the first characterized example of a...

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