Human p53 restores DNA synthesis control in fission yeast.
The p53 gene is the most common target for genetic alterations in human 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. Here we report the construction and characterization of a p53 wild type expression strain of fission yeast. Upon induction of wild type p53 expression a dosage dependent growth arrest was observed rendering recipient yeast cells sensitive to UV irradiation in a p53 dosage dependent fashion. The observed growth arrest was efficiently suppressed by coexpression of human CDC25C phosphatase, which restored a normal resistance to UV irradiation in p53 and CDC25C coexpressing yeast cells. Furthermore, expression of CDC25C alone inactivated the DNA synthesis control whereas p53 and CDC25C coexpressing yeast cells showed an intact checkpoint control. Upon moderate expression of wild type p53 a restoration of the DNA synthesis control was also observed in a cdc2.3w mutant background, whereas a tumor mutant of p53 failed to restore this important checkpoint in fission yeast.
Bureik
M
M
Medical Biochemistry, University of Saarland, Homburg/Saar, Germany.
Jungbluth
A
A
Drescher
R
R
Wagner
P
P
D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D004261:DNA Replication; D004271:DNA, Fungal / Q000096:biosynthesis*; D015870:Gene Expression; D006801:Humans; D008938:Mitosis; D016296:Mutagenesis; D016196:S Phase; D012568:Schizosaccharomyces / Q000235:genetics* / Q000254:growth & development; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*; D020687:cdc25 Phosphatases
D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D016159:Tumor Suppressor Protein p53; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases