[HTML][HTML] Different telomere damage signaling pathways in human and mouse cells

A Smogorzewska, T de Lange - The EMBO journal, 2002 - embopress.org
A Smogorzewska, T de Lange
The EMBO journal, 2002embopress.org
Programmed telomere shortening in human somatic cells is thought to act as a tumor
suppressor pathway, limiting the replicative potential of developing tumor cells. Critically
short human telomeres induce senescence either by activating p53 or by inducing the
p16/RB pathway, and suppression of both pathways is required to suppress senescence of
aged human cells. Here we report that removal of TRF2 from human telomeres and the
ensuing de‐protection of chromosome ends induced immediate premature senescence …
Programmed telomere shortening in human somatic cells is thought to act as a tumor suppressor pathway, limiting the replicative potential of developing tumor cells. Critically short human telomeres induce senescence either by activating p53 or by inducing the p16/RB pathway, and suppression of both pathways is required to suppress senescence of aged human cells. Here we report that removal of TRF2 from human telomeres and the ensuing de‐protection of chromosome ends induced immediate premature senescence. Although the telomeric tracts remained intact, the TRF2 ΔBΔM‐induced premature senescence was indistinguishable from replicative senescence and could be mediated by either the p53 or the p16/RB pathway. Telomere de‐protection also induced a growth arrest and senescent morphology in mouse cells. However, in this setting the loss of p53 function was sufficient to completely abrogate the arrest, indicating that the p16/RB response to telomere dysfunction is not active in mouse cells. These findings reveal a fundamental difference in telomere damage signaling in human and mouse cells that bears on the use of mouse models for the telomere tumor suppressor pathway.
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