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Science 311 (5758): 226-229

Copyright © 2006 by the American Association for the Advancement of Science

PER-TIM Interactions in Living Drosophila Cells: An Interval Timer for the Circadian Clock

Pablo Meyer, Lino Saez, Michael W. Young*

Abstract: In contrast to current models, fluorescence resonance energy transfer measurements using a single-cell imaging assay with fluorescent forms of PER and TIM showed that these proteins bind rapidly and persist in the cytoplasm while gradually accumulating in discrete foci. After ~6 hours, complexes abruptly dissociated, as PER and TIM independently moved to the nucleus in a narrow time frame. The perL mutation delayed nuclear accumulation in vivo and in our cultured cell system, but without affecting rates of PER/TIM assembly or dissociation. This finding points to a previously unrecognized form of temporal regulation that underlies 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}

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