p53 deficiency does not affect the accumulation of point mutations in a transgene target.
DNA repair is required by organisms to prevent the accumulation of mutations and to maintain the integrity of genetic information. Mammalian cells that have been treated with agents that damage DNA have an increase in p53 levels, a p53-dependent arrest at G1 in the cell cycle, and a p53-dependent apoptotic response. It has been hypothesized that this block in cell cycle progression is necessary to allow time for DNA repair or to direct the damaged cell to an apoptotic pathway. This hypothesis predicts that p53-deficient cells would have an abnormal apoptotic response and exhibit a "mutator" phenotype. Using a sensitive assay for the accumulation of point mutations, small deletions, and insertions, we have directly tested whether p53-deficient cells exhibit an increased frequency of mutation before and after exposure to DNA-damaging agents. We report that wild-type and p53-deficient fibroblasts, thymocytes, and tumor tissue have indistinguishable rates of point mutation accumulation in a transgenic lacI target gene. These results suggest that the role of p53 in G1 checkpoint control and tumor suppression does not affect the accumulation of point mutations.
Sands
A T
AT
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Suraokar
M B
MB
Sanchez
A
A
Marth
J E
JE
Donehower
L A
LA
Bradley
A
A
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D010582:Bacteriophage lambda / Q000235:genetics; D002478:Cells, Cultured; D029968:Escherichia coli Proteins; D005822:Genetic Vectors; D056968:Lac Repressors; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D017354:Point Mutation; D012097:Repressor Proteins / Q000235:genetics; D017384:Sequence Deletion; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000502:physiology
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D056968:Lac Repressors; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53