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Molecular Biology and Genetics |
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, [F. B., K. W. K., B. V., C. L.] and the Howard Hughes Medical Institute [B. V.], Johns Hopkins University, Baltimore, Maryland 21231; Institute of Anthropology and Human Genetics, University of Munich, Munich 80333, Germany [C. F., M. R. S.]; and Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912 [A. D., J. M. S.]
Because p53 mutation and aneuploidy usually coexist, it has been suggested that p53 inactivation leads to aneuploidy. We have rigorously tested this hypothesis in diploid human cell lines in which p53 was experimentally inactivated by targeted homologous recombination. Cells completely deficient in p53 did not become aneuploid, although a slight tendency toward tetraploidization was observed. No increased rates of numerical or structural chromosomal instabilities were observed in the p53-deficient cells. Rates of sister chromatid exchange and homologous recombination were also unaffected by p53 status. These results show that inactivation of p53 does not, in and of itself, lead to the development of aneuploidy.
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