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Cellular senescence and organismal ageing in the absence of p21 CIP1/WAF1 in ku80 −/− mice
Author(s) -
Zhao Bo,
Benson Erica K,
Qiao Ruifang,
Wang Xing,
Kim Sunchin,
Manfredi James J,
Lee Sam W,
Aaronson Stuart A
Publication year - 2009
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2008.220
Subject(s) - ku80 , senescence , biology , ageing , dna damage , phenotype , microbiology and biotechnology , dna , genetics , gene , dna binding protein , transcription factor
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.