Interacting Molecular Loops in the Mammalian Circadian Clock

May 12, 2000Science (New York, N.Y.)

Molecular feedback loops working together in the mammal's internal daily clock

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Abstract

In the mouse, the core mechanism for the master circadian clock involves interacting positive and negative feedback loops.

  • Analysis of specific mutant mice indicates substantially altered Bmal1 rhythms.
  • PERIOD2 is identified as a key positive regulator of the Bmal1 loop.
  • CRYPTOCHROMES are shown to act as negative regulators for the Period and Cryptochrome cycles.
  • Inhibition of CLOCK:BMAL1-mediated transcription by CRYPTOCHROME occurs through direct protein interactions, independent of other proteins.

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