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Telomere elongation in immortal human cells without detectable telomerase activity
T M Bryan1, A Englezou, J Gupta
1Cancer Research Group, Children's Medical Research Institute, Westmead, Sydney, NSW, Australia.
The EMBO Journal
|September 1, 1995
Summary
Cell immortalization doesn't always require telomerase activation. Some immortal cells maintain very long telomeres without detectable telomerase, suggesting alternative stabilization mechanisms are crucial for cell longevity.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Cellular immortality is often linked to telomerase reactivation.
- Telomerase adds repeats to telomeres, counteracting shortening during cell division.
Purpose of the Study:
- To investigate if telomerase activation is essential for human cell immortalization.
- To explore alternative mechanisms of telomere maintenance in immortal cells.
Main Methods:
- Assessed telomerase activity in normal fibroblasts, pre-crisis transformed cells, and immortalized cell lines.
- Generated and analyzed hybrids between telomerase-negative and telomerase-positive cells.
- Examined telomere length and heterogeneity in various cell types.
Main Results:
- Normal and pre-crisis cells lacked telomerase activity.
- 15 out of 35 immortalized cell lines were telomerase-negative but had very long, heterogeneous telomeres.
- Hybrids between telomerase-negative and positive cells initially senesced, with some later immortalizing with or without telomerase.
Conclusions:
- Telomerase activation is not strictly necessary for cell immortalization.
- Lengthened or stabilized telomeres appear essential for immortalization.
- Alternative, non-telomerase mechanisms may contribute to telomere maintenance and cell immortality.