Dataset Information


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

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.


PROVIDER: S-EPMC2613205 | BioStudies | 2009-01-01

REPOSITORIES: biostudies

Similar Datasets

2014-01-01 | S-EPMC3989187 | BioStudies
1000-01-01 | S-EPMC3491824 | BioStudies
1000-01-01 | S-EPMC3763444 | BioStudies
1000-01-01 | S-EPMC2063673 | BioStudies
2013-01-01 | S-EPMC3776094 | BioStudies
2013-01-01 | S-EPMC3827076 | BioStudies
2015-01-01 | S-EPMC4359307 | BioStudies
2009-01-01 | S-EPMC2692066 | BioStudies
1000-01-01 | S-EPMC3041166 | BioStudies
2009-01-01 | S-EPMC2615166 | BioStudies