Telomerase activity does not always imply telomere maintenance

Michel M. Ouellette, Dara L. Aisner, Isabelle Savre-Train, Woodring E. Wright, Jerry W. Shay

Research output: Contribution to journalArticle

97 Scopus citations

Abstract

The forced expression of the catalytic subunit of human telomerase, hTERT, produces telomerase activity, allows telomere maintenance, and extends the cellular life span of IMR90 human lung fibroblasts. The mutation D869A abolishes both the catalytic activity of hTERT and its ability to extend cellular life span, demonstrating that the immortalizing capabilities of the enzyme are dependent on active catalysis. A second mutant of hTERT was examined that contains three copies of an HA epitope inserted at the C-terminus. This mutant produced telomerase activity in fibroblasts that was virtually indistinguishable from that of wild type telomerase when assayed in vitro. However, the forced expression of this mutant failed to maintain telomeres or extend cellular life span. Our results show that the catalytic activity of hTERT is required for cellular immortalization but that the presence of active telomerase does not necessarily imply telomere maintenance and immortality.

Original languageEnglish (US)
Pages (from-to)795-803
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume254
Issue number3
DOIs
StatePublished - Jan 27 1999
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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