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p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2
J Karlseder1, D Broccoli, Y Dai
1Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10021, USA. Cell Genesys, Foster City, CA 94405, USA.
Science (New York, N.Y.)
|February 26, 1999
Summary
Natural chromosome ends (telomeres) normally avoid apoptosis. However, inhibiting telomeric-repeat binding factor 2 (TRF2) triggers cell death, suggesting telomeres can signal apoptosis.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Natural chromosome ends (telomeres) are protected from apoptosis.
- Broken chromosomes typically induce programmed cell death (apoptosis).
Purpose of the Study:
- To investigate the role of telomeric-repeat binding factor 2 (TRF2) in suppressing apoptosis at telomeres.
- To understand the signaling pathways involved when telomere protection is compromised.
Main Methods:
- Inhibition of TRF2 in mammalian cell types.
- Analysis of apoptosis induction.
- Assessment of p53 and ATM kinase involvement.
- Investigation of dicentric chromosome formation.
Main Results:
- TRF2 inhibition induced apoptosis in some mammalian cells.
- The apoptosis pathway involved p53 and ATM kinase, indicating DNA damage response activation.
- Apoptosis was not caused by chromosome fusions, but directly by telomeres lacking TRF2.
- Telomeres lacking TRF2 may directly signal apoptosis, resembling damaged DNA.
Conclusions:
- TRF2 is crucial for preventing apoptosis at natural chromosome ends.
- Compromised telomere protection can lead to cell death, potentially via a DNA damage-like signal.
- Telomere shortening might trigger cell death instead of senescence in certain cellular contexts.
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