p53- and ATM-Dependent Apoptosis Induced by Telomeres Lacking TRF2
1999; American Association for the Advancement of Science; Volume: 283; Issue: 5406 Linguagem: Inglês
10.1126/science.283.5406.1321
ISSN1095-9203
AutoresJan Karlseder, Dominique Broccoli, Yumin Dai, Stephen Hardy, Titia de Lange,
Tópico(s)Cancer-related Molecular Pathways
ResumoAlthough 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.
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