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- Title
p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2.
- Authors
Karlseder, J; Broccoli, D; Dai, Y; Hardy, S; de Lange, T
- Abstract
Although broken chromosomes can induce apoptosis, natural chromosome ends (telomeres) do not trigger this response. It is shown that this suppression of apoptosis involves the telomeric-repeat binding factor 2 (TRF2). Inhibition of TRF2 resulted in apoptosis in a subset of mammalian cell types. The response was mediated by p53 and the ATM (ataxia telangiectasia mutated) kinase, consistent with activation of a DNA damage checkpoint. Apoptosis was not due to rupture of dicentric chromosomes formed by end-to-end fusion, indicating that telomeres lacking TRF2 directly signal apoptosis, possibly because they resemble damaged DNA. Thus, in some cells, telomere shortening may signal cell death rather than senescence.
- Publication
Science (New York, N.Y.), 1999, Vol 283, Issue 5406, p1321
- ISSN
0036-8075
- Publication type
Journal Article
- DOI
10.1126/science.283.5406.1321