Light-Induced Degradation of TIMELESS and Entrainment of the Drosophila Circadian Clock

@article{Myers1996LightInducedDO,
  title={Light-Induced Degradation of TIMELESS and Entrainment of the Drosophila Circadian Clock},
  author={Michael P. Myers and Karen Wager-Smith and Adrian Rothenfluh-Hilfiker and Michael W. Young},
  journal={Science},
  year={1996},
  volume={271},
  pages={1736 - 1740}
}
Two genes, period (per) and timeless (tim), are required for production of circadian rhythms in Drosophila. The proteins encoded by these genes (PER and TIM) physically interact, and the timing of their association and nuclear localization is believed to promote cycles of per and tim transcription through an autoregulatory feedback loop. Here it is shown that TIM protein may also couple this molecular pacemaker to the environment, because TIM is rapidly degraded after exposure to light. TIM… 
Light-dependent sequestration of TIMELESS by CRYPTOCHROME.
TLDR
CRYPTOCHROME (CRY), a protein involved in circadian photoperception in Drosophila, is shown to block the function of PERIOD/TIMELESS (PER/Tim) heterodimeric complexes in a light-dependent fashion.
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TLDR
The members of the photolyase/cryptochrome family contain flavin adenine dinucleotide (FAD) as chromophore and are involved in two diverse functions, DNA repair and photoreception of environmental light signals.
Differential Effects of Light and Heat on theDrosophila Circadian Clock Proteins PER and TIM
TLDR
These findings can account for the lack of apparent steady-state shifts in Drosophila behavioral rhythms by heat pulses applied in the late night and strongly suggest that stimulus-induced changes in the speed of circadian clocks can contribute to phase-shifting responses.
Altered Entrainment and Feedback Loop Function Effected by a Mutant Period Protein
TLDR
It is reported here that a hypophosphorylated mutant PER protein, produced by creating a small internal deletion, displays increased stability and low-amplitude oscillations, consistent with previous reports that phosphorylation is required for protein turnover.
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.
The molecular control of circadian behavioral rhythms and their entrainment in Drosophila.
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  • Medicine, Biology
    Annual review of biochemistry
  • 1998
TLDR
The recent discovery of PER homologues in mice and humans suggests that a related mechanism controls mammalian circadian behavioral rhythms.
Light-Induced Resetting of a Mammalian Circadian Clock Is Associated with Rapid Induction of the mPer1 Transcript
TLDR
In both the phasing of dark expression and the response to light mPer1 is most similar to the Neurospora clock gene frq, consistent with the localization of both light-sensitive and light-insensitive oscillators in this circadian center.
CULLIN-3 Controls TIMELESS Oscillations in the Drosophila Circadian Clock
TLDR
CUL-3 is a new component of the Drosophila clock, which plays an important role in the control of TIM oscillations and shows additive effects on TIM and PER, suggesting different roles for the two ubiquitination complexes on PER and TIM cycling.
CK1/Doubletime activity delays transcription activation in the circadian clock
TLDR
The results indicate that phosphorylation of PER residue S589 stabilizes and activates PER inhibitory function in the presence of TIM, but promotes PER degradation in its absence.
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.
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References

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Rhythmic Expression of timeless: A Basis for Promoting Circadian Cycles in period Gene Autoregulation
TLDR
The clock gene timeless (tim) is required for circadian rhythmicity in Drosophila and the cyclic expression of tim appears to dictate the timing of PER protein accumulation and nuclear localization, suggesting that tim promotes circadian rhythms of per and tim transcription by restricting per RNA and PERprotein accumulation to separate times of day.
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.
Loss of circadian behavioral rhythms and per RNA oscillations in the Drosophila mutant timeless.
TLDR
A clock mutation, timeless (tim), is described that produces arrhythmia for bothClosion and locomotor activity of adults occur rhythmically in Drosophila melanogaster with a circadian period of about 24 hours.
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.
Temporal phosphorylation of the Drosophila period protein.
TLDR
It is suggested that the phosphorylation status of PER is an important determinant in the Drosophila clock's time-keeping mechanism.
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TLDR
The frequency (frq) locus of Neurospora crassa is shown to encode a central component in a molecular feedback loop in which the product of frq negatively regulated its own transcript, which resulted in a daily oscillation in the amount offrq transcript.
Light-induced resetting of a circadian clock is mediated by a rapid increase in frequency transcript
TLDR
The effects of light on a gene known to encode a state variable of a circadian oscillator, the frequency (frq) gene, are examined to explain how a simple unidirectional signal may be turned into a bidirectional clock response.
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.
Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels
TLDR
Observations indicate that the cycling of per-encoded protein could result from per RNA cycling, and that there is a feedback loop through which the activity of each per gene product causes cycling of its own RNA.
Circadian rhythms in drosophila can be driven by period expression in a restricted group of central brain cells
TLDR
It is demonstrated that expression of per under the control of the glass promoter confers both behavioral and molecular rhythmicity.
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