Related Experiment Videos
Immortalized cells with no detectable telomerase activity. A review
R R Reddel1, T M Bryan, J P Murnane
1Children's Medical Research Institute, Sydney, NSW, Australia. rreddel@mail.usyd.edu.au
Biochemistry. Biokhimiia
|February 19, 1998
Summary
Human cells can become immortal without telomerase by using alternative lengthening of telomeres (ALT) mechanisms. These ALT pathways are crucial for telomere maintenance and cell immortalization in telomerase-negative cells.
Area of Science:
- Cell biology
- Genetics
- Molecular biology
Background:
- Cellular immortalization is typically linked to telomerase activity.
- Some immortalized human cells lack detectable telomerase activity.
- Telomere lengthening occurs even in the absence of telomerase.
Purpose of the Study:
- Investigate alternative mechanisms for telomere lengthening in immortal cells.
- Understand telomere maintenance in telomerase-negative cell lines.
- Explore the hypothesis that telomere maintenance (telomerase or ALT) is essential for immortalization.
Main Methods:
- Comparison of terminal restriction fragment (TRF) patterns before and after immortalization.
- Analysis of telomere length heterogeneity and dynamics.
- Observing telomere dynamics in ALT cell lines using proximal markers.
Main Results:
- Telomere lengthening occurs in immortal cells lacking telomerase activity.
- Telomerase-negative immortal cells exhibit extreme telomere length heterogeneity.
- ALT cell lines show a pattern of telomere shortening followed by rapid elongation.
Conclusions:
- Alternative Lengthening of Telomeres (ALT) is a key mechanism for immortalization in telomerase-negative cells.
- ALT likely involves a non-reciprocal recombinational mechanism.
- Telomere maintenance, either by telomerase or ALT, is a prerequisite for cellular immortalization.