| | |  | | | | Record from Web of Science® | | | | | | |
| Interacting molecular loops in the mammalian circadian clock |
|
|
| Author(s): Shearman LP, Sriram S, Weaver DR, Maywood ES, Chaves I, Zheng BH, Kume K, Lee CC, van der Horst GTJ, Hastings MH, Reppert SM |
| Source: SCIENCE Volume: 288 Issue: 5468 Pages: 1013-1019 Published: MAY 12 2000 |
| Times Cited: 524 References: 44 |
| 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 Small 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Reppert, SM (reprint author), Massachusetts Gen Hosp, Massachusetts Gen Hosp Children, Lab Dev Chronobiol, Boston, MA 02114 USA |
Addresses:
1. Massachusetts Gen Hosp, Massachusetts Gen Hosp Children, Lab Dev Chronobiol, Boston, MA 02114 USA
2. Harvard Univ, Sch Med, Boston, MA 02114 USA
3. Univ Cambridge, Dept Anat, Cambridge CB2 3DY, England
4. Erasmus Univ, Dept Cell Biol & Genet, Ctr Med Genet, NL-3000 DR Rotterdam, Netherlands
5. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA |
| Publisher: AMER ASSOC ADVANCEMENT SCIENCE, 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 313EY |
| ISSN: 0036-8075 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |