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

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Science  13 Jan 2006:
Vol. 311, Issue 5758, pp. 226-229
DOI: 10.1126/science.1118126

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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.

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