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Overview
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Background
Circadian Clocks are biological timepieces that regulate hormonal rhythms, sleep cycles and feeding behaviors. These rhythms are generated in the superchiasmatic nucleus (SCN), a cell-autonomous circadian oscillator located within the brain that is synchronized with the environment by light. A number of transcription factors, including Clock and BMAL1, are molecular components of the SCN that induce the expression of proteins involved in light/dark cycle entrainment, which include Per1 and Per2. Tim, for timeless, generates a negative feedback loop that regulates the activity of Clock by suppressing the expression of Clock target genes. Tim forms heterodimers with Per1 and Per2 that bind Clock and block the activation of Clock-BMAL1 dimers to repress Per gene expression. Additionally, the CRY proteins, which are cryptochrome photoreceptors for the circadian Clock, function as light-independent inhibitors of the circadian Clock. CRY1 and CRY2 negatively regulate SCN components by associating with the activators Clock-BMAL1, and also with the various feedback inhibitors Per1, Per2 and Tim.
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