Cellular senescence and organismal ageing in the absence of p21CIP1/WAF1 in ku80−/− mice |
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| Authors: | Bo Zhao Erica K Benson Ruifang Qiao Xing Wang Sunchin Kim James J Manfredi Sam W Lee Stuart A Aaronson |
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| Institution: | 1. Department of Oncological Sciences, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, New York, 10029‐6574 USA;2. Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, Massachusetts, USA |
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| 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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