Cellular and molecular basis of circadian timing in mammals.

In mammals, a master circadian clock resides in the suprachiasmatic nuclei of the anterior hypothalamus. The suprachiasmatic nuclei is composed of multiple, single-cell circadian oscillators, which, when synchronized, lead to coordinated circadian outputs that ultimately regulate overt rhythms. Several "clock genes" have been cloned that are involved in interacting transcriptional/translational feedback loops that comprise the molecular clockwork. The daily light-dark cycle ultimately impinges on the control of 2 clock genes that reset the core clock mechanism. Output genes are also generated by the central clock mechanism, but their protein products transduce downstream effects. Greater understanding of the cellular and molecular control of the suprachiasmatic nuclei provides opportunities for pharmacological manipulation of circadian timing.

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