Analysis of ku80-Mutant Mice and Cells with Deficient Levels of p53
AUTOR(ES)
Lim, Dae-Sik
FONTE
American Society for Microbiology
RESUMO
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 γ-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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85695Documentos Relacionados
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