Telomeres are favoured targets of a persistentDnA damage response in ageing andstress-induced senescence

摘要

Telomeres are specialized nucleoprotein structures, which protect chromosome ends and havebeen implicated in the ageing process. Telomere shortening has been shown to contributeto a persistent DnA damage response (DDR) during replicative senescence, the irreversibleloss of division potential of somatic cells. similarly, persistent DDR foci can be found instress-induced senescence, although their nature is not understood. Here we show, usingimmuno-fluorescent in situ hybridization and ChIP, that up to half of the DnA damage foci instress-induced senescence are located at telomeres irrespective of telomerase activity. moreover,live-cell imaging experiments reveal that all persistent foci are associated with telomeres.Finally, we report an age-dependent increase in frequencies of telomere-associated foci in gutand liver of mice, occurring irrespectively of telomere length. We conclude that telomeres areimportant targets for stress in vitro and in vivo and this has important consequences for theageing process.