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- Title
Interacting molecular loops in the mammalian circadian clock.
- Authors
Shearman, L P; Sriram, S; Weaver, D R; Maywood, E S; Chaves, I; Zheng, B; Kume, K; Lee, C C; van der Horst, G T; Hastings, M H; Reppert, S M
- 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.
- Publication
Science (New York, N.Y.), 2000, Vol 288, Issue 5468, p1013
- ISSN
0036-8075
- Publication type
Journal Article
- DOI
10.1126/science.288.5468.1013