p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2

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), Inhibit ion of TRF2 resulted in apoptosis in a subset of mammalian cell types, The response was mediated by p53 and the ATM (ataxia telangiectasia mutated) ki nase, consistent with activation of a DNA damage checkpoint. Apoptosis was not due to rupture of dicentric chromosomes formed by end-to-end fusion, in dicating that telomeres Lacking TRF2 directly signal apoptosis, possibly be cause they resemble damaged DNA. Thus, in some cells, telomere shortening m ay signal cell death rather than senescence.