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Science 3 November 1995:
Vol. 270. no. 5237, pp. 808 - 810
DOI: 10.1126/science.270.5237.808
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Reports

Rhythmic Expression of timeless: A Basis for Promoting Circadian Cycles in period Gene Autoregulation

Amita Sehgal (1),  Adrian Rothenfluh-Hilfiker,  Melissa Hunter-Ensor,  Yifeng Chen,  Michael P. Myers,  Michael W. Young

The clock gene timeless (tim) is required for circadian rhythmicity in Drosophila. The accumulation of tim RNA followed a circadian rhythm, and the phase and period of the tim RNA rhythm were indistinguishable from those that have been reported for per. The tim RNA oscillations were found to be dependent on the presence of PER and TIM proteins, which demonstrates feedback control of tim by a mechanism previously shown to regulate per expression. The cyclic expression of tim appears to dictate the timing of PER protein accumulation and nuclear localization, suggesting that tim promotes circadian rhythms of per and tim transcription by restricting per RNA and PER protein accumulation to separate times of day.


A. Sehgal, M. Hunter-Ensor, Y. Chen, Department of Neuroscience and Center for Sleep and Respiratory Neurobiology, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA.
A. Rothenfluh-Hilfiker, 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.
(1) To whom correspondence should be addressed.


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Quantitative Analysis of Drosophila period Gene Transcription in Living Animals.
J. D. Plautz, M. Straume, R. Stanewsky, C. F. Jamison, C. Brandes, H. B. Dowse, J. C. Hall, and S. A. Kay (1997)
J Biol Rhythms 12, 204-217
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S. K. Crosthwaite, J. C. Dunlap, and J. J. Loros (1997)
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Rhythms of Drosophila period gene expression in culture.
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J Biol Rhythms 12, 157-172
   Abstract »    PDF »
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   Abstract »    Full Text »    PDF »
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   Full Text »    PDF »
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   Abstract »    PDF »
Molecular Anatomy of a Light-sensitive Circadian Pacemaker in Drosophila.
M.W. Young, K. Wager-Smith, L. Vosshall, L. Saez, and M.P. Myers (1996)
Cold Spring Harb Symp Quant Biol 61, 279-284
   Abstract »    PDF »
Forward Genetic Approaches to Circadian Clocks in Mice.
D.P. King and J.S. Takahashi (1996)
Cold Spring Harb Symp Quant Biol 61, 295-302
   Abstract »    PDF »
Positional Cloning and Sequence Analysis of the Drosophila Clock Gene, timeless.
M. P. Myers, K. Wager-Smith, C. S. Wesley, M. W. Young, and A. Sehgal (1995)
Science 270, 805-808
   Abstract »    PDF »
Isolation of timeless by PER Protein Interaction: Defective Interaction Between timeless Protein and Long-Period Mutant PER^L.
N. Gekakis, L. Saez, A.-M. Delahaye-Brown, M. P. Myers, A. Sehgal, M. W. Young, and C. J. Weitz (1995)
Science 270, 811-815
   Abstract »    PDF »
Oscillation and Light Induction of timeless mRNA in the Mammalian Circadian Clock.
S. A. Tischkau, J. A. Barnes, F.-J. Lin, E. M. Myers, J. W. Soucy, E. L. Meyer-Bernstein, W. J. Hurst, P. W. Burgoon, D. Chen, A. Sehgal, et al. (1999)
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   Abstract »    Full Text »    PDF »


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