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MBC in Press, published online ahead of print December 7, 2005
Mol. Biol. Cell 10.1091/mbc.E05-09-0903

A more recent version of this article appeared on February 1, 2006
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Submitted on September 29, 2005
Revised on November 22, 2005
Accepted on November 28, 2005

Cell Cycle-regulated Trafficking of Human Telomerase to Telomeres

Rebecca L. Tomlinson, Tania D. Ziegler, Teerawit Supakorndej, Rebecca M. Terns, and Michael P. Terns

Departments of Biochemistry and Molecular Biology and Genetics, University of Georgia, Athens, GA 30602

Monitoring Editor: Marvin P. Wickens

Telomerase synthesizes telomeres at the ends of human chromosomes during S phase. The results presented here suggest that telomerase activity may be regulated by intranuclear trafficking of the key components of the enzyme in human cells. We examined the subcellular localization of endogenous human telomerase RNA (hTR) and telomerase reverse transcriptase (hTERT) in HeLa cervical carcinoma cells. Throughout most of the cell cycle, we found that the two essential components of telomerase accumulate at intranuclear sites separate from telomeres. However, during S phase, both hTR and hTERT are specifically recruited to subsets of telomeres. The localization of telomerase to telomeres is dynamic, peaking at midS phase. We also found complex associations of both hTR and hTERT with nucleoli and Cajal bodies during S phase, implicating both structures in the biogenesis and trafficking of telomerase. Our results mark the first observation of human telomerase at telomeres, and provide a mechanism for the cell cycle-dependent regulation of telomere synthesis in human cells.

Address correspondence to: Rebecca M. Terns (rterns{at}bmb.uga.edu) or Michael P. Terns (mterns{at}bmb.uga.edu)




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