The human CRY1 tail controls circadian timing by regulating its association with CLOCK:BMAL1

Oct 27, 2020Proceedings of the National Academy of Sciences of the United States of America

The human CRY1 tail controls body clock timing by managing its interaction with the CLOCK:BMAL1 complex

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Abstract

The CRY1Δ11 mutant may lengthen circadian period, causing delayed sleep phase disorder (DSPD).

  • Mutations in core clock genes can alter circadian periods.
  • CRY1 functions as a repressor by inhibiting the activity of CLOCK:BMAL1.
  • The CRY1 tail, particularly the region encoded by exon 11, influences the interaction between the PHR domain and CLOCK:BMAL1.
  • The PHR-binding site in exon 11 is necessary to disrupt CRY1's interaction with CLOCK.
  • Interactions between the PHR domain and the tail are preserved in the related protein CRY2 and are reduced when either CRY is bound to the corepressor PERIOD2.
  • The autoregulatory role of the CRY1 tail and its interactions may be functionally conserved across different species.

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Full Text

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