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

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.
Publisher
AMER SOC MICROBIOLOGY
Issue Date
2000-06
Language
ENG
Keywords

SEVERE COMBINED IMMUNODEFICIENCY; STRAND BREAK REPAIR; X-RAY RESISTANCE; V(D)J RECOMBINATION; DNA-REPAIR; KU86-DEFICIENT MICE; P53-DEFICIENT MICE; SCID MUTATION; PROTEIN; CANCER

Citation

MOLECULAR AND CELLULAR BIOLOGY, v.20, no.11, pp.3772 - 3780

ISSN
0270-7306
DOI
10.1128/MCB.20.11.3772-3780.2000
URI
http://hdl.handle.net/10203/74825
Appears in Collection
BS-Journal Papers(저널논문)
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