HUMAN P53 RESTORES DNA-SYNTHESIS CONTROL IN FISSION YEAST

The p53 gene is the most common target for genetic alterations in huma n cancers. As a transcriptional regulator p53 enhances the expression of proteins that control cellular proliferation. Although there is no evidence of a p53 homologous gene in yeast, the p53 protein was found to be functional in terms of growth repression and transactivation in yeast, suggesting that some features of p53 function are conserved. He re we report the construction and characterization of a p53 wild type expression strain of fission yeast. Upon induction of wild type p53 ex pression a dosage dependent growth arrest was observed rendering recip ient yeast cells sensitive to UV irradiation in a p53 dosage dependent fashion. The observed growth arrest was efficiently suppressed by coe xpression of human CDC25C phosphatase, which restored a normal resista nce to UV irradiation in p53 and CDC25C coexpressing yeast cells. Furt hermore, expression of CDC25C alone inactivated the DNA synthesis cont rol whereas p53 and CDC25C coexpressing yeast cells showed an intact c heckpoint control. Upon moderate expression of wild type p53 a restora tion of the DNA synthesis control was also observed in a cdc2.3w mutan t background, whereas a tumor mutant of p53 failed to restore this imp ortant checkpoint in fission yeast.