Targeted inactivation of p53 in human cells does not result in aneuploidy.
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.
Bunz
Fred
F
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University, Baltimore, Maryland 21231, USA.
Fauth
Christine
C
Speicher
Michael R
MR
Dutriaux
Annie
A
Sedivy
John M
JM
Kinzler
Kenneth W
KW
Vogelstein
Bert
B
Lengauer
Christoph
C
D000483:Alleles; D000782:Aneuploidy; D002872:Chromosome Deletion; D003110:Colonic Neoplasms / Q000235:genetics*; D005347:Fibroblasts / Q000502:physiology / Q000648:ultrastructure; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011995:Recombination, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics
D016159:Tumor Suppressor Protein p53