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EMBO Rep. 2009 Jan;10(1):71-8. doi: 10.1038/embor.2008.220. Epub 2008 Dec 12.

Cellular senescence and organismal ageing in the absence of p21(CIP1/WAF1) in ku80(-/-) mice.

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  • 1Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.

Erratum in

  • EMBO Rep. 2011 Mar;12(3):283.

Abstract

Ku80 is important in the repair of DNA double-strand breaks by its essential function in non-homologous end-joining. The absence of Ku80 causes the accumulation of DNA damage and leads to premature ageing in mice. We showed that mouse embryonic fibroblasts (MEFs) from ku80(-/-) mice senesced rapidly with elevated levels of p53 and p21. Deletion of p21 delayed the early senescence phenotype in ku80(-/-) MEFs, despite an otherwise intact response of p53. In contrast to ku80(-/-)p53(-/-) mice, which die rapidly primarily from lymphomas, there was no significant increase in tumorigenesis in ku80(-/-)p21(-/-) mice. However, ku80(-/-)p21(-/-) mice showed no improvement with respect to rough fur coat or osteopaenia, and even showed a shortened lifespan compared with ku80(-/-) mice. These results show that the increased lifespan of ku80(-/-) MEFs owing to the loss of p21 is not associated with an improvement of the premature ageing phenotypes of ku80(-/-) mice observed at the organismal level.

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