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

Research output: Contribution to journalArticle

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

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    Masutomi, K., Yu, E. Y., Khurts, S., Ben-Porath, I., Currier, J. L., Metz, G. B., Brooks, M. W., Kaneko, S., Murakami, S., DeCaprio, J. A., Weinberg, R. A., Stewart, S. A., & Hahn, W. C. (2003). Telomerase maintains telomere structure in normal human cells. Cell, 114(2), 241-253. https://doi.org/10.1016/S0092-8674(03)00550-6