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PER-TIM Interactions in Living Drosophila Cells: An Interval Timer for the Circadian Clock
Pablo Meyer,Lino Saez,Michael W. Young*
In contrast to current models, fluorescence resonance energytransfer measurements using a single-cell imaging assay withfluorescent forms of PER and TIM showed that these proteinsbind rapidly and persist in the cytoplasm while gradually accumulatingin discrete foci. After 6 hours, complexes abruptly dissociated,as PER and TIM independently moved to the nucleus in a narrowtime frame. The perL mutation delayed nuclear accumulation invivo and in our cultured cell system, but without affectingrates of PER/TIM assembly or dissociation. This finding pointsto a previously unrecognized form of temporal regulation thatunderlies the periodicity of the circadian clock.
Laboratory of Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
* To whom correspondence should be addressed. E-mail: young{at}rockefeller.edu
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TIMELESS Is an Important Mediator of CK2 Effects on Circadian Clock Function In Vivo.
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Rhythmic E-Box Binding by CLK-CYC Controls Daily Cycles in per and tim Transcription and Chromatin Modifications.
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