In order to avoid replicative senescence, tumor cells must acquire a telomere maintenance mechanism.Beside telomerase activation, a minority of tumors employs a recombinational mechanism called Alternative Lengthening of Telomeres (ALT).Several studies have investigated the potential ALT stimulation 3 Piece King Panel HB w/Storage FB by inactivation of ATRX in tumor cells, obtaining contrasting results.
Differently, since ALT can be viewed as a mechanism to overcome telomere shortening-mediated replicative senescence, we have investigated the effects of the inhibition of ATRX and p53 in aging primary fibroblasts.We observed that senescence leads to a phenotype that seems permissive for ALT activity, i.e.
high levels of ALT-associated PML bodies (APB), telomeric damage and telomeric cohesion.On the other hand, RAD51 is highly repressed and thus telomeric recombination, upon which the ALT machinery vibrators-kits relies, is almost absent.Silencing of ATRX greatly increases telomeric recombination in young cells, but is not able to overcome senescence-induced repression of homologous recombination.
Conversely, inhibition of both p53 and ATRX leads to a phenotype reminiscent of some aspects of ALT activity, with a further increase of APB, a decrease of telomere shortening (and increased proliferation) and, above all, an increase of telomeric recombination.