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p53- and ATM-Dependent Apoptosis Induced by Telomeres Lacking TRF2

Science  26 Feb 1999:
Vol. 283, Issue 5406, pp. 1321-1325
DOI: 10.1126/science.283.5406.1321

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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.

  • * These authors contributed equally to this work.

  • Present address: Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA.

  • Present address: Chiron Corporation, 4560 Horton Street, Mailstop 4-3, Emeryville, CA 94608–2916, USA.

  • § To whom correspondence should be addressed. E-mail: delange{at}rockvax.rockefeller.edu

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