| First Author | Shearman LP | Year | 2000 |
| Journal | Science | Volume | 288 |
| Issue | 5468 | Pages | 1013-9 |
| PubMed ID | 10807566 | Mgi Jnum | J:62075 |
| Mgi Id | MGI:1858302 | Doi | 10.1126/science.288.5468.1013 |
| Citation | Shearman LP, et al. (2000) Interacting molecular loops in the mammalian circadian clock [see comments]. Science 288(5468):1013-9 |
| abstractText | 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. |
