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CLOCK stabilizes CYCLE to initiate clock function in Drosophila.

Tianxin Liu1,2, Guruswamy Mahesh1,2, Wangjie Yu1,2

  • 1Department of Biology, Texas A&M University, College Station, TX 77845-3258.

Proceedings of the National Academy of Sciences of the United States of America
|October 5, 2017
PubMed
Summary

The Drosophila circadian clock requires CLOCK (CLK) to stabilize CYCLE (CYC) protein, enabling ectopic clock function. CLOCK, CYCLE, and CRYPTOCHROME (CRY) expression are sufficient to initiate circadian rhythms in naive cells.

Keywords:
CYCLEDrosophilacircadian clockcryptochromeprotein stability

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Area of Science:

  • Chronobiology
  • Molecular Biology
  • Genetics

Background:

  • The Drosophila circadian clock relies on transcriptional feedback loops initiated by CLOCK-CYCLE (CLK-CYC) heterodimers.
  • Circadian clocks are typically found in specific neurons and peripheral tissues, but can be induced in other cells.

Purpose of the Study:

  • To investigate the mechanisms governing the initiation of circadian clock function in Drosophila.
  • To determine the genetic requirements for inducing ectopic circadian clocks in non-canonical clock cells.

Main Methods:

  • Utilized cell culture and in vivo experiments in Drosophila.
  • Investigated protein-protein interactions and gene expression in nonclock cells.

Main Results:

  • Demonstrated that CLK binds to and stabilizes CYC protein in both cell culture and in vivo.
  • Showed that ectopic clocks require CRYPTOCHROME (CRY), essential for light entrainment and peripheral clock function.
  • Confirmed that CLK, CYC, and CRY expression is sufficient to drive clock function in naive cells.

Conclusions:

  • Established the genetic architecture for initiating Drosophila circadian clock function.
  • Revealed conserved mechanisms of circadian activator stability across eukaryotes.
  • Identified CLK, CYC, and CRY as sufficient components to establish circadian clocks in naive cells.