Dual modes of CLOCK:BMAL1 inhibition mediated by Cryptochrome and Period proteins in the mammalian circadian clock

Sep 18, 2014Genes & development

Two ways that Cryptochrome and Period proteins block the CLOCK:BMAL1 complex in the mammalian body clock

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Abstract

CRY is identified as the primary repressor in the circadian clock's transcription-translation feedback loop.

  • CRY binds to CLOCK-BMAL1 at the promoter and inhibits transcription without dissociating from the complex.
  • This type of repression by CRY is referred to as 'blocking'-type repression.
  • PER alone does not affect CLOCK-BMAL1-activated transcription.
  • In the presence of CRY, PER can inhibit transcription by displacing CLOCK-BMAL1 from the promoter, termed 'displacement'-type repression.
  • These findings suggest that the negative regulation of the circadian clock operates through two distinct mechanisms.

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