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experiments define the genetic architecture required to initiate circadian clock function in Drosophila, reveal mechanisms governing circadian activator stability that are conserved in perhaps all eukaryotes, and suggest that Clk, cyc, and cry expression is sufficient to drive clock expression in naive cells
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propose that the dCLK/CYC-controlled TTFL operates differently in subsets of pacemaker neurons, which may contribute to their specific functions
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ClkAR mutants showed significantly faster age-related locomotor deficits. Accelerated locomotor decline of the ClkAR mutant required expression of the PDF receptor and correlated to an apparent loss of dopaminergic neurons in the brain
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Here we demonstrate that the transcription factor CLOCKWORK ORANGE (CWO) antagonizes CLK-CYC E-box binding, thus enhancing the removal of CLK-CYC from E-boxes to maintain transcriptional repression. This process requires PER, which suggests that PER-TIM and CWO cooperate to maintain a transcriptionally repressed state by removing CLK-CYC from E-boxes
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these results demonstrate a key role of Clk post-transcriptional control in stabilizing circadian transcription.
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Our findings suggest a novel role for clock protein phosphorylation in governing the relative strengths of entraining modalities by adjusting the dynamics of circadian gene expression.
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These results demonstrate that CLK phosphorylation influences the circadian period by regulating CLK activity and progression through the feedback loop.
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Computational dissection of CLK/CYC context-specific binding sites reveals sequence motifs for putative partner factors, which are predictive for individual binding sites
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usp8 loss of function (RNAi) or expression of a dominant-negative form of the protein (USP8-DN) enhances CLK/CYC transcriptional activity and alters fly locomotor activity rhythms
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CLK has specific targets in different tissues, implying that important CLK partner proteins and/or mechanisms contribute to gene-specific and tissue-specific regulation
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CTRIP destabilizes CLK protein in a PER-independent manner and helps degradation of phosphorylated PER and TIM in the morning
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dPER(DeltaCBD) does not provoke the daily hyperphosphorylation of dCLOCK, indicating that direct interactions between dPER and dCLOCK are necessary for the dCLOCK phosphorylation
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findings show that Clk and cyc act during starvation to modulate the conflict of whether flies sleep or search for food
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Here we examined the consequences of loss of clock function on reproductive fitness in Drosophila melanogaster with mutated period (per(0)), timeless (tim(0)), cycle (cyc(0)), and Clock (Clk(Jrk)) genes
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dCLK levels are critical in mediating the direct photostimulation of locomotor activity in Drosophila.
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Stress response genes protect against lethal effects of sleep deprivation in Drosophila
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role for VRI in the rhythmic repression of output genes that cycle in phase with Clk
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Clk, vri, and Pdp-1 have roles in controlling Drosophila circadian oscillations, as shown in a simulation
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PER-dependent rhythms in CLK phosphorylation control rhythms in E-box-dependent transcription and CLK stability, thus linking PER and CLK function during the circadian cycle
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constitutive levels of nuclear CLK regulate rhythmic transcription in circadian oscillator cells and CLK contributes to other behavioral processes by regulating gene expression in non-oscillator cells
