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Originally published In Press as doi:10.1074/jbc.M002843200 on April 27, 2000

J. Biol. Chem., Vol. 275, Issue 26, 19719-19722, June 30, 2000
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Telomere Shortening Is Proportional to the Size of the G-rich Telomeric 3'-Overhang*

Kenneth E. HuffmanDagger , Stephen D. LeveneDagger , Valerie M. Tesmer§, Jerry W. Shay§, and Woodring E. Wright§

From the Dagger  Department of Molecular and Cell Biology, University of Texas at Dallas, Richardson, Texas 75083 and the § Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9039

Most normal diploid human cells do not express telomerase activity and are unable to maintain telomere length with ongoing cell divisions. We show that the length of the single-stranded G-rich telomeric 3'-overhang is proportional to the rate of shortening in four human cell types that exhibit different rates of telomere shortening in culture. These results provide direct evidence that the size of the G-rich overhang is not fixed but subject to regulation. The potential ability to manipulate this rate has profound implications both for slowing the rate of replicative aging in normal cells and for accelerating the rate of telomere loss in cancer cells in combination with anti-telomerase therapies.

* This work was supported by National Institutes of Health Grants AGO1228 (to W. E. W.) and GM47898 and GM55871 (to S. D. L.) and by an American Cancer Society postdoctoral fellowship (to V. M. T.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Cell Biology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9039. Tel.: 214-648-2933; Fax: 214-648-8696; E-mail: wright@utsw.swmed.edu.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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