Analysis of ku80-mutant mice and cells with deficient levels of p53

Dae Sik Lim, Hannes Vogel, Dennis M. Willerford, Arthur T. Sands, Kenneth A. Platt, Paul Hasty

Research output: Contribution to journalArticlepeer-review

139 Scopus citations


Absence of Ku80 results in increased sensitivity to ionizing radiation, defective lymphocyte development, early onset of an age-related phenotype, and premature replicative senescence. Here we investigate the role of p53 on the phenotype of ku80-mutant mice and cells. Reducing levels of p53 increased the cancer incidence for ku80(-/-) mice. About 20% of ku80(-/-) p53(+/-) mice developed a broad spectrum of cancer by 40 weeks and all ku80(-/-) p53(-/-) mice developed pro-B-cell lymphoma by 16 weeks. Reducing levels of p53 rescued populations of ku80(-/-) cells from replicative senescence by enabling spontaneous immortalization. The double-mutant cells are impaired for the G1/S checkpoint due to the p53 mutation and are hypersensitive to χ-radiation and reactive oxygen species due to the Ku80 mutation. These data show that replicative senescence is caused by a p53-dependent cell cycle response to damaged DNA in ku80(-/-) cells and that p53 is essential for preventing very early onset of pro-B-cell lymphoma in ku80(-/-) mice.

Original languageEnglish (US)
Pages (from-to)3772-3780
Number of pages9
JournalMolecular and cellular biology
Issue number11
StatePublished - Jun 2000
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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