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Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence
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Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence
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Journal Article
Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence
2012
Overview
Telomeres are specialized nucleoprotein structures, which protect chromosome ends and have been implicated in the ageing process. Telomere shortening has been shown to contribute to a persistent DNA damage response (DDR) during replicative senescence, the irreversible loss of division potential of somatic cells. Similarly, persistent DDR foci can be found in stress-induced senescence, although their nature is not understood. Here we show, using immuno-fluorescent
in situ
hybridization and ChIP, that up to half of the DNA damage foci in stress-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 gut and liver of mice, occurring irrespectively of telomere length. We conclude that telomeres are important targets for stress
in vitro
and
in vivo
and this has important consequences for the ageing process.
Irreparable DNA damage leads to apoptosis or senescence. Hewitt
et al
. show that, in response to genotoxic or oxidative stress, DNA damage occurs predominantly at telomere associated foci, which accumulate with age
in vivo
, irrespective of telomerase activity.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Pub. Group
