| First Author | Lim DS | Year | 2000 |
| Journal | Mol Cell Biol | Volume | 20 |
| Issue | 11 | Pages | 3772-80 |
| PubMed ID | 10805721 | Mgi Jnum | J:62142 |
| Mgi Id | MGI:1858377 | Doi | 10.1128/mcb.20.11.3772-3780.2000 |
| Citation | Lim DS, et al. (2000) Analysis of ku80-mutant mice and cells with deficient levels of p53. Mol Cell Biol 20(11):3772-80 |
| abstractText | 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 G(1)/S checkpoint due to the p53 mutation and are hypersensitive to gamma-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. |
