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
TLDR
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.
The Drosophila double-timeS Mutation Delays the Nuclear Accumulation of period Protein and Affects the Feedback Regulation of period mRNA
TLDR
Results suggest that dbt can regulate the feedback of per protein on its mRNA by delaying the time at which it is translocated to nuclei and altering the level of nuclear PER during the declining phase of the cycle.
A PER/TIM/DBT interval timer for Drosophila's circadian clock.
TLDR
It is suggested that a cytoplasmic interval timer regulates nuclear translocation of PER/TIM/Doubletime (DBT) and TIM proteins, which are involved in the generation of circadian behavior in Drosophila.
Phosphorylation of PERIOD Is Influenced by Cycling Physical Associations of DOUBLE-TIME, PERIOD, and TIMELESS in the Drosophila Clock
TLDR
The varying associations of PER, DBT and TIM appear to determine the onset and duration of nuclear PER function within the Drosophila clock.
A TIMELESS-Independent Function for PERIOD Proteins in the Drosophila Clock
TLDR
In the absence of TIM, nuclear PER can function as a potent negative transcriptional regulator and Conversion of PER/TIM heterodimers to nuclear PER proteins appears to be required to complete transcriptional repression and terminate each circadian molecular cycle.
Short-period mutations of per affect a double-time-dependent step in the Drosophila circadian clock
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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References

SHOWING 1-10 OF 110 REFERENCES
The Drosophila Clock Gene double-time Encodes a Protein Closely Related to Human Casein Kinase Iε
TLDR
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.
A Mutant Drosophila Homolog of Mammalian Clock Disrupts Circadian Rhythms and Transcription of period and timeless
TLDR
The mutant phenotype results from a premature stop codon that eliminates much of the putative activation domain of this bHLH-PAS transcription factor, thus explaining the dominant features of Jrk and strongly supports common clock components present in the common ancestor of Drosophila and mammals.
CYCLE Is a Second bHLH-PAS Clock Protein Essential for Circadian Rhythmicity and Transcription of Drosophila period and timeless
TLDR
It is proposed that the CYC:CLK heterodimer binds to per and tim E boxes and makes a major contribution to the circadian transcription of Drosophila clock genes.
Block in nuclear localization of period protein by a second clock mutation, timeless.
TLDR
The studies described here indicate that the nuclear localization of PER is blocked by timeless (tim), a second chromosome mutation that, like per null mutations, abolishes circadian rhythms.
Regulation of the Drosophila Protein Timeless Suggests a Mechanism for Resetting the Circadian Clock by Light
TLDR
The cyclic expression of TIM protein in adult heads is shown and it lags behind peak levels of TIM RNA by several hours, suggesting that TIM mediates light-induced resetting of the circadian clock.
The timSL Mutant of the Drosophila Rhythm Gene timeless Manifests Allele-Specific Interactions with period Gene Mutants
TLDR
The identification of this first period-altering tim allele provides further evidence that TIM is a major component of the clock, and the allele-specific interactions with PER provide evidence that the PER/TIM heterodimer is a unit of circadian function.
Suppression of PERIOD protein abundance and circadian cycling by the Drosophila clock mutation timeless.
TLDR
The tim mutant constitutively produces a low level of PER protein that is comparable with that produced late in the day by wild‐type flies and it is suggested that the multiple effects of tim are due to a primary effect on per expression at the posttranscriptional level.
Temporally regulated nuclear entry of the Drosophila period protein contributes to the circadian clock
TLDR
The data indicate that regulation of PER nuclear entry is critical for circadian oscillations by providing a necessary temporal delay between PER synthesis and its effect on transcription.
Isolation of timeless by PER Protein Interaction: Defective Interaction Between timeless Protein and Long-Period Mutant PERL
TLDR
The cloning of complementary DNAs derived from the tim gene in a two-hybrid screen for PER-interacting proteins and the demonstration of a physical interaction between the tim protein (TIM) and PER in vitro are reported.
A light-entrainment mechanism for the Drosophila circadian clock
TLDR
The Per–Tim complex is a functional unit of the Drosophila circadian clock, and Tim degradation may be the initial response of the clock to light.
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