Light-Independent Role of CRY1 and CRY2 in the Mammalian Circadian Clock

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Science  22 Oct 1999:
Vol. 286, Issue 5440, pp. 768-771
DOI: 10.1126/science.286.5440.768

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Cryptochrome (CRY), a photoreceptor for the circadian clock in Drosophila, binds to the clock component TIM in a light-dependent fashion and blocks its function. In mammals, genetic evidence suggests a role for CRYs within the clock, distinct from hypothetical photoreceptor functions. Mammalian CRY1 and CRY2 are here shown to act as light-independent inhibitors of CLOCK-BMAL1, the activator driving Per1 transcription. CRY1 or CRY2 (or both) showed light-independent interactions with CLOCK and BMAL1, as well as with PER1, PER2, and TIM. Thus, mammalian CRYs act as light-independent components of the circadian clock and probably regulate Per1transcriptional cycling by contacting both the activator and its feedback inhibitors.

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