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Science 22 October 1999:
Vol. 286. no. 5440, pp. 768 - 771
DOI: 10.1126/science.286.5440.768
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Reports

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

Edmund A. Griffin Jr., David Staknis, Charles J. Weitz *

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 Per1 transcriptional cycling by contacting both the activator and its feedback inhibitors.

Department of Neurobiology, Harvard Medical School, Boston, MA 02115 USA.
*   To whom correspondence should be addressed. E-mail: cweitz{at}hms.harvard.edu

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The Basic Helix-Loop-Helix-PAS Protein MOP9 Is a Brain-Specific Heterodimeric Partner of Circadian and Hypoxia Factors.
J. B. Hogenesch, Y.-Z. Gu, S. M. Moran, K. Shimomura, L. A. Radcliffe, J. S. Takahashi, and C. A. Bradfield (2000)
J. Neurosci. 20, RC83
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Clock Genes in the Heart : Characterization and Attenuation With Hypertrophy.
M. E. Young, P. Razeghi, and H. Taegtmeyer (2001)
Circ. Res. 88, 1142-1150
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Science. ISSN 0036-8075 (print), 1095-9203 (online)