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Telomerase activity does not always imply telomere maintenance
M M Ouellette1, D L Aisner, I Savre-Train
1Department of Cell Biology and Neuroscience, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas, 75235-9039, USA.
Biochemical and Biophysical Research Communications
|January 28, 1999
Summary
Forced expression of human telomerase (hTERT) can extend cell life, but only if its catalytic activity is intact. Active telomerase doesn't always guarantee telomere maintenance or cell immortality.
Area of Science:
- Molecular Biology
- Cell Biology
- Gerontology
Background:
- Telomeres protect chromosome ends and shorten with each cell division.
- Cellular senescence, or aging, is linked to telomere shortening.
- Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase, an enzyme that can maintain telomere length.
Purpose of the Study:
- To investigate the role of hTERT catalytic activity in cellular immortalization and telomere maintenance.
- To determine if active telomerase is sufficient for extending cellular lifespan and maintaining telomeres.
Main Methods:
- Forced expression of wild-type hTERT and hTERT mutants in IMR90 human lung fibroblasts.
- Assaying telomerase activity in vitro.
- Evaluating telomere length and cellular lifespan.
- Utilizing a catalytically inactive hTERT mutant (D869A) and an epitope-tagged hTERT mutant.
Main Results:
- Wild-type hTERT expression led to telomere maintenance and extended cellular lifespan.
- The catalytically inactive hTERT mutant (D869A) failed to maintain telomeres or extend lifespan.
- An epitope-tagged hTERT mutant showed in vitro activity similar to wild-type but did not maintain telomeres or extend lifespan in cells.
- These findings indicate a dissociation between in vitro telomerase activity and in vivo cellular effects.
Conclusions:
- Catalytic activity of hTERT is essential for its immortalizing function.
- The presence of active telomerase in cells does not automatically ensure telomere maintenance or cellular immortality.
- Cellular immortalization by hTERT requires more than just detectable telomerase enzymatic activity.