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Interlocked Feedback Loops Within the Drosophila Circadian Oscillator

Science  22 Oct 1999:
Vol. 286, Issue 5440, pp. 766-768
DOI: 10.1126/science.286.5440.766

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Abstract

Drosophila Clock (dClk) is rhythmically expressed, with peaks in mRNA and protein (dCLK) abundance early in the morning. dClk mRNA cycling is shown here to be regulated by PERIOD-TIMELESS (PER-TIM)–mediated release of dCLK- and CYCLE (CYC)–dependent repression. Lack of both PER-TIM derepression and dCLK-CYC repression results in high levels of dClk mRNA, which implies that a separate dClk activator is present. These results demonstrate that the Drosophila circadian feedback loop is composed of two interlocked negative feedback loops: aper-tim loop, which is activated by dCLK-CYC and repressed by PER-TIM, and a dClk loop, which is repressed by dCLK-CYC and derepressed by PER-TIM.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: phardin{at}uh.edu

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