Molecular mechanism of the repressive phase of the mammalian circadian clock

Jan 14, 2021Proceedings of the National Academy of Sciences of the United States of America

Molecular process controlling the inactive phase of the mammal's daily biological clock

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Abstract

CRY-PER is associated with increased local concentrations of CK1δ at CLOCK-BMAL1-bound promoters.

  • CRY-PER participates in the repression of CLOCK-BMAL1 activity through a displacement mechanism.
  • CK1δ is recruited to the nucleus by CRY-PER, affecting CLOCK-BMAL1 function.
  • An increased local concentration of CK1δ at promoters/enhancers may enhance the phosphorylation of CLOCK.
  • Phosphorylation of CLOCK is linked to the dissociation of CLOCK-BMAL1 and CRY from the E-box.
  • These observations provide clarity regarding the dynamic repressive phase of the circadian clock system.

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