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

TLDR

Natural chromosome ends (telomeres) normally do not trigger apoptosis, unlike broken chromosomes. Loss of TRF2 activates p53‑ and ATM‑dependent apoptosis in certain mammalian cells, indicating that telomeres lacking TRF2 directly signal cell death rather than senescence.

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.