Telomerase maintains telomere structure in normal human cells

Kenkichi Masutomi, Evan Y. Yu, Shilagardy Khurts, Ittai Ben-Porath, Jennifer L. Currier, Geoffrey B. Metz, Mary W. Brooks, Shuichi Kaneko, Seishi Murakami, James A. DeCaprio, Robert A. Weinberg, Sheila A. Stewart, William C. Hahn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

666 Scopus citations

Abstract

In normal human cells, telomeres shorten with successive rounds of cell division, and immortalization correlates with stabilization of telomere length. These observations suggest that human cancer cells achieve immortalization in large part through the illegitimate activation of telomerase expression. Here, we demonstrate that the rate-limiting telomerase catalytic subunit hTERT is expressed in cycling primary presenescent human fibroblasts, previously believed to lack hTERT expression and telomerase activity. Disruption of telomerase activity in normal human cells slows cell proliferation, restricts cell lifespan, and alters the maintenance of the 3′ single-stranded telomeric overhang without changing the rate of overall telomere shortening. Together, these observations support the view that telomerase and telomere structure are dynamically regulated in normal human cells and that telomere length alone is unlikely to trigger entry into replicative senescence.

Original languageAmerican English
Pages (from-to)241-253
Number of pages13
JournalCell
Volume114
Issue number2
DOIs
StatePublished - 25 Jul 2003
Externally publishedYes

Bibliographical note

Funding Information:
We thank Ronald DePinho, Richard Maser, Richard Possemato, and Mauro Zappaterra for helpful comments and members of the Hahn lab for discussions. We also thank Steve Lessnick for help with the shRNA retroviral vector. R.A.W. is an American Cancer Society Research Professor and a Daniel K. Ludwig Cancer Research Professor. This work was supported in part by grants from the National Cancer Institute to W.C.H. (K01 CA94223), S.A.S. (F32 CA93033), and R.A.W. (R01 CA78461); an EMBO Long-Term Fellowship (I.B.-P.); a grant from MIT/Merck and Co., Inc. (R.A.W.); a Doris Duke Clinical Scientist Development Award (W.C.H.); and a Kimmel Scholar Award (W.C.H.).

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