p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2 |
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Authors: | Karlseder J Broccoli D Dai Y Hardy S de Lange T |
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Institution: | Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10021, USA. Cell Genesys, Foster City, CA 94405, USA. |
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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. |
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