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

Lookup NU author(s): Dr Graeme Hewitt, Dr Diana Jurk, Francisco Marques, Clara Correia Melo, Dr Timothy Hardy, Dr Agata Page, Rhys Anderson, Morgan Taschuk, Professor Jelena Mann, Dr Joao Passos

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Abstract

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.


Publication metadata

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

Journal: Nature Communications

Year: 2012

Volume: 3

Issue: 2

Print publication date: 28/02/2012

ISSN (electronic): 2041-1723

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ncomms1708

DOI: 10.1038/ncomms1708


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