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Science 3 November 1995:
Vol. 270. no. 5237, pp. 811 - 815
DOI: 10.1126/science.270.5237.811
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Reports

Isolation of timeless by PER Protein Interaction: Defective Interaction Between timeless Protein and Long-Period Mutant PER

Nicholas Gekakis,  Lino Saez,  Anne-Marie Delahaye-Brown,  Michael P. Myers,  Amita Sehgal,  Michael W. Young,  Charles J. Weitz (1)

The period (per) gene likely encodes a component of the Drosophila circadian clock. Circadian oscillations in the abundance of per messenger RNA and per protein (PER) are thought to arise from negative feedback control of per gene transcription by PER. A recently identified second clock locus, timeless (tim), apparently regulates entry of PER into the nucleus. Reported here are the cloning of complementary DNAs derived from the tim gene in a two-hybrid screen for PER-interacting proteins and the demonstration of a physical interaction between the tim protein (TIM) and PER in vitro. A restricted segment of TIM binds directly to a part of the PER dimerization domain PAS. PER^L, a mutation that causes a temperature-sensitive lengthening of circadian period and a temperature-sensitive delay in PER nuclear entry, exhibits a temperature-sensitive defect in binding to TIM. These results suggest that the interaction between TIM and PER determines the timing of PER nuclear entry and therefore the duration of part of the circadian cycle.


N. Gekakis, A.-M. Delahaye-Brown, C. J. Weitz, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
L. Saez, M. P. Myers, M. W. Young, Howard Hughes Medical Institute, National Science Foundation Science and Technology Center for Biological Timing, and the Laboratory of Genetics, Rockefeller University, New York, NY 10021, USA.
A. Sehgal, Department of Neuroscience and the Center for Sleep and Respiratory Neurobiology, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA.
(1) To whom correspondence should be addressed.


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