double-time Is a Novel Drosophila Clock Gene that Regulates PERIOD Protein Accumulation

@article{Price1998doubletimeIA,
  title={double-time Is a Novel Drosophila Clock Gene that Regulates PERIOD Protein Accumulation},
  author={Jeffrey L. Price and Justin Blau and Adrian Rothenfluh and Marla Abodeely and Brian Kloss and Michael W. Young},
  journal={Cell},
  year={1998},
  volume={94},
  pages={83-95}
}
We have isolated three alleles of a novel Drosophila clock gene, double-time (dbt). Short- (dbtS) and long-period (dbtL) mutants alter both behavioral rhythmicity and molecular oscillations from previously identified clock genes, period and timeless. A third allele, dbtP, causes pupal lethality and eliminates circadian cycling of per and tim gene products in larvae. In dbtP mutants, PER proteins constitutively accumulate, remain hypophosphorylated, and no longer depend on TIM proteins for their… 

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The Drosophila Clock Gene double-time Encodes a Protein Closely Related to Human Casein Kinase Iε
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TLDR
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TLDR
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TLDR
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TLDR
The results suggest that short-period per mutations, and mutations of dbt, affect the same molecular step that controls nuclear PER turnover, and conclude that, in wild-type flies, the previously defined PER'short domain' may regulate the activity of DBT on PER.
Kinetics of Doubletime Kinase-dependent Degradation of the Drosophila Period Protein*
TLDR
The study provides a simple model in which the changes in Drosophila behavioral rhythms can be explained solely by changes in the rate of PER degradation, which resembles that with wild-type DBT.
The Double-Time Protein Kinase Regulates the Subcellular Localization of the Drosophila Clock Protein Period
TLDR
In this study, control of PER subcellular localization in Drosophila clock cells in vivo is examined and it is found that PER can translocate to the nucleus in tim01 null mutants but only if DBT kinase activity is inhibited, and nuclear PER is a potent transcriptional repressor in dbt mutants in vivo without TIM.
TIMELESS‐dependent positive and negative autoregulation in the Drosophila circadian clock
TLDR
Analysis of period (per) mRNA levels and transcription uncovered a novel role for TIM in clock regulation: TIM increases per mRNA levels through a post‐transcriptional mechanism.
Drosophila doubletime Mutations Which either Shorten or Lengthen the Period of Circadian Rhythms Decrease the Protein Kinase Activity of Casein Kinase I
TLDR
Low enzyme activity is associated with both short-period and long-period phenotypes of DBT in Drosophila melanogaster.
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DBT is capable of binding to PER in vitro and in Drosophila cells, suggesting that a physical association of PER and DBT regulates PER phosphorylation and accumulation in vivo.
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