Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 17 October 2003:
Vol. 302. no. 5644, pp. 439 - 442
DOI: 10.1126/science.1086593
Prev | Table of Contents | Next

Reports

Requirement of Mammalian Timeless for Circadian Rhythmicity

Jessica W. Barnes,1* Shelley A. Tischkau,1,2* Jeffrey A. Barnes,1* Jennifer W. Mitchell,1 Penny W. Burgoon,1 Jason R. Hickok,1 Martha U. Gillette1{dagger}

Despite a central circadian role in Drosophila for the transcriptional regulator Timeless (dTim), the relevance of mammalian Timeless (mTim) remains equivocal. Conditional knockdown of mTim protein expression in the rat suprachiasmatic nucleus (SCN) disrupted SCN neuronal activity rhythms, and altered levels of known core clock elements. Full-length mTim protein (mTIM-fl) exhibited a 24-hour oscillation, where as a truncated isoform (mTIM-s) was constitutively expressed. mTIM-fl associated with the mammalian clock Period proteins (mPERs) in oscillating SCN cells. These data suggest that mTim is required for rhythmicity and is a functional homolog of dTim on the negative-feedback arm of the mammalian molecular clockwork.

1 Department of Cell and Structural Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
2 Department of Veterinary Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.



* These authors contributed equally to this study.

{dagger} To whom correspondence should be addressed. E-mail: mgillett{at}uiuc.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Loss of cryptochrome reduces cancer risk in p53 mutant mice.
N. Ozturk, J. H. Lee, S. Gaddameedhi, and A. Sancar (2009)
PNAS 106, 2841-2846
   Abstract »    Full Text »    PDF »
Casein kinase I{varepsilon} Does Not Rescue double-time Function in Drosophila Despite Evolutionarily Conserved Roles in the Circadian Clock.
T. Sekine, T. Yamaguchi, K. Hamano, M. W. Young, M. Shimoda, and L. Saez (2008)
J Biol Rhythms 23, 3-15
   Abstract »    PDF »
Natural plasticity in circadian rhythms is mediated by reorganization in the molecular clockwork in honeybees.
Y. Shemesh, M. Cohen, and G. Bloch (2007)
FASEB J 21, 2304-2311
   Abstract »    Full Text »    PDF »
Tel2 Is Required for Activation of the Mrc1-mediated Replication Checkpoint.
M. Shikata, F. Ishikawa, and J. Kanoh (2007)
J. Biol. Chem. 282, 5346-5355
   Abstract »    Full Text »    PDF »
Role of Phosphorylation in the Mammalian Circadian Clock.
K. Vanselow and A. Kramer (2007)
Cold Spring Harb Symp Quant Biol 72, 167-176
   Abstract »    PDF »
Principles and Problems Revolving Round Rhythm-related Genetic Variants.
J. C. Hall, D. C. Chang, and E. Dolezelova (2007)
Cold Spring Harb Symp Quant Biol 72, 215-232
   Abstract »    PDF »
Molecular and phylogenetic analyses reveal mammalian-like clockwork in the honey bee (Apis mellifera) and shed new light on the molecular evolution of the circadian clock.
E. B. Rubin, Y. Shemesh, M. Cohen, S. Elgavish, H. M. Robertson, and G. Bloch (2006)
Genome Res. 16, 1352-1365
   Abstract »    Full Text »    PDF »
Genetic Analysis of Saccharomyces cerevisiae H2A Serine 129 Mutant Suggests a Functional Relationship Between H2A and the Sister-Chromatid Cohesion Partners Csm3-Tof1 for the Repair of Topoisomerase I-Induced DNA Damage.
C. Redon, D. R. Pilch, and W. M. Bonner (2006)
Genetics 172, 67-76
   Abstract »    Full Text »    PDF »
Differential Control of Bmal1 Circadian Transcription by REV-ERB and ROR Nuclear Receptors.
F. Guillaumond, H. Dardente, V. Giguere, and N. Cermakian (2005)
J Biol Rhythms 20, 391-403
   Abstract »    PDF »
Cryptochrome, Circadian Cycle, Cell Cycle Checkpoints, and Cancer.
M. A. Gauger and A. Sancar (2005)
Cancer Res. 65, 6828-6834
   Abstract »    Full Text »    PDF »
Deregulated expression of the PER1, PER2 and PER3 genes in breast cancers.
S.-T. Chen, K.-B. Choo, M.-F. Hou, K.-T. Yeh, S.-J. Kuo, and J.-G. Chang (2005)
Carcinogenesis 26, 1241-1246
   Abstract »    Full Text »    PDF »
The Double-Time Protein Kinase Regulates the Subcellular Localization of the Drosophila Clock Protein Period.
S. A. Cyran, G. Yiannoulos, A. M. Buchsbaum, L. Saez, M. W. Young, and J. Blau (2005)
J. Neurosci. 25, 5430-5437
   Abstract »    Full Text »    PDF »
Coupling of Human Circadian and Cell Cycles by the Timeless Protein.
K. Unsal-Kacmaz, T. E. Mullen, W. K. Kaufmann, and A. Sancar (2005)
Mol. Cell. Biol. 25, 3109-3116
   Abstract »    Full Text »    PDF »
Long-Term Constant Light Induces Constitutive Elevated Expression of mPER2 Protein in the Murine SCN: A Molecular Basis for Aschoff's Rule?.
M. Munoz, S. N. Peirson, M. W. Hankins, and R. G. Foster (2005)
J Biol Rhythms 20, 3-14
   Abstract »    PDF »
Swi1 and Swi3 Are Components of a Replication Fork Protection Complex in Fission Yeast.
E. Noguchi, C. Noguchi, W. H. McDonald, J. R. Yates III, and P. Russell (2004)
Mol. Cell. Biol. 24, 8342-8355
   Abstract »    Full Text »    PDF »
Transcription Regulation within the Circadian Clock: The E-box and Beyond.
P. E. Hardin (2004)
J Biol Rhythms 19, 348-360
   Abstract »    PDF »
Clock Genes, Oscillators, and Cellular Networks in the Suprachiasmatic Nuclei.
M. H. Hastings and E. D. Herzog (2004)
J Biol Rhythms 19, 400-413
   Abstract »    PDF »
Clock Gene Evolution and Functional Divergence.
E. Tauber, K. S. Last, P. J.W. Olive, and C. P. Kyriacou (2004)
J Biol Rhythms 19, 445-458
   Abstract »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)