Abstract
TIMELESS has a clear role in the regulation of circadian rhythms in Drosophila, but its role in mammalian circadian regulation remains unclear. A mutation identified in a small family with advanced sleep phase causes cytoplasmic accumulation of TIMELESS. We confirm that TIMELESS can bind the critical negative regulators of the circadian clock, PER2 and CRY2, and destabilize them when TIMELESS remains in the cytoplasm. The mutant mouse model has a phase advance of sleep-wake behavior and altered sensitivity to light pulses, but normal period length. These data demonstrate that TIMELESS may play a role in regulating minor phase changes and therefore contribute to the maintenance of circadian rhythmicity in mammals.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- June 2019
- DOI:
- Bibcode:
- 2019PNAS..11612045K