Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence

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  2. Graeme Hewitt
  3. Dr Diana Jurk
  4. Francisco Marques
  5. Clara Correia Melo
  6. Dr Timothy Hardy
  7. Dr Agata Page
  8. Rhys Anderson
  9. Morgan Taschuk
  10. Dr Jelena Mann
  11. Dr Joao Passos
Author(s)Hewitt G, Jurk D, Marques FDM, Correia-Melo C, Hardy T, Gackowska A, Anderson R, Taschuk M, Mann J, Passos JF
Publication type Article
JournalNature Communications
Year2012
Volume3
Issue2
Pages
ISSN (electronic)2041-1723
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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.
PublisherNature Publishing Group
URLhttp://dx.doi.org/10.1038/ncomms1708
DOI10.1038/ncomms1708
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