| First Author | Zhao B | Year | 2009 |
| Journal | EMBO Rep | Volume | 10 |
| Issue | 1 | Pages | 71-8 |
| PubMed ID | 19079133 | Mgi Jnum | J:143043 |
| Mgi Id | MGI:3822689 | Doi | 10.1038/embor.2008.220 |
| Citation | Zhao B, et al. (2009) Cellular senescence and organismal ageing in the absence of p21(CIP1/WAF1) in ku80(-/-) mice. EMBO Rep 10(1):71-8 |
| abstractText | 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. |
