Interacting Molecular Loops in the Mammalian Circadian Clock
Top Cited Papers
- 12 May 2000
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 288 (5468), 1013-1019
- https://doi.org/10.1126/science.288.5468.1013
Abstract
We show that, in the mouse, the core mechanism for the master circadian clock consists of interacting positive and negative transcription and translation feedback loops. Analysis of Clock/Clock mutant mice, homozygous Period2 Brdm1 mutants, and Cryptochrome -deficient mice reveals substantially altered Bmal1 rhythms, consistent with a dominant role of PERIOD2 in the positive regulation of the Bmal1 loop. In vitro analysis of CRYPTOCHROME inhibition of CLOCK: BMAL1-mediated transcription shows that the inhibition is through direct protein:protein interactions, independent of the PERIOD and TIMELESS proteins. PERIOD2 is a positive regulator of the Bmal1 loop, and CRYPTOCHROMES are the negative regulators of the Period and Cryptochrome cycles.Keywords
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