+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Interacting molecular loops in the mammalian circadian clock

Interacting molecular loops in the mammalian circadian clock

Science 288(5468): 1013-1019

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 Period2Brdm1 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. Copyright 2000 by the AAAS.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 003480866

Download citation: RISBibTeXText

PMID: 10807566

DOI: 10.1126/science.288.5468.1013

Related references

Circadian rhythms. Two feedback loops run mammalian clock. Science 288(5468): 943-944, 2000

Tuning the mammalian circadian clock: robust synergy of two loops. Plos Computational Biology 7(12): E1002309, 2012

Feedback Loops of the Mammalian Circadian Clock Constitute Repressilator. Plos Computational Biology 12(12): E1005266, 2016

Deciphering the Dynamics of Interlocked Feedback Loops in a Model of the Mammalian Circadian Clock. Biophysical Journal 115(10): 2055-2066, 2018

Molecular mechanisms of the mammalian circadian clock: identifying the clock genes. 2007

Dual roles of FBXL3 in the mammalian circadian feedback loops are important for period determination and robustness of the clock. Proceedings of the National Academy of Sciences of the United States of America 110(12): 4750-4755, 2013

Molecular mechanism of cell-autonomous circadian gene expression of Period2, a crucial regulator of the mammalian circadian clock. Molecular Biology of the Cell 17(2): 555-565, 2005

Tuning the period of the mammalian circadian clock: additive and independent effects of CK1εTau and Fbxl3Afh mutations on mouse circadian behavior and molecular pacemaking. Journal of Neuroscience 31(4): 1539-1544, 2011

The mammalian circadian clock protein period counteracts cryptochrome in phosphorylation dynamics of circadian locomotor output cycles kaput (CLOCK). Journal of Biological Chemistry 289(46): 32064-32072, 2015

Clock genes and light-induced resetting of circadian clock: Dichotomy in mammalian circadian center. Sleep and Biological Rhythms 2(1 Supplement): S38-S39, 2004

Molecular components of the Mammalian circadian clock. Handbook of Experimental Pharmacology 2013(217): 3-27, 2013

Molecular analysis of the mammalian circadian clock. European Journal of Neuroscience 12(Supplement 11): 1, 2000

Molecular signals of Mammalian circadian clock. Kobe Journal of Medical Sciences 50(3-4): 101-109, 2005

Molecular mechanism of mammalian circadian clock. Journal of Biochemistry 134(6): 777-784, 2004

Molecular architecture of the mammalian circadian clock. Trends in Cell Biology 24(2): 90-99, 2014