Suppression of the Yeast Mutation rft1-1 by Human p53

Mutations in the gene encoding p53 have been found to be the most common genetic alterations in human cancer. p53 is thought to exert its function of tumor suppression through inhibition of cell proliferation or induction of apoptosis in response to DNA damage. Although there have been no proteins homologous to p53 identified in lower eucaryotic organisms, it is known that overexpression of wild-type human p53 can inhibit cell growth of Schizosaccharomyces pombe and Saccharomyces cerevisiae (Bischoff et al., 1992; Nigro et al., 1992), suggesting that certain aspects of p53 function may manifest or exist in yeast. In an attempt to identify the p53-like proteins in the yeast S. cerevisiae, we isolated a mutant that requires wild-type p53 for its viability. The mutant, rft1-1, is defective in cell cycle progression and arrests before mitosis when p53 protein is depleted. Genetic and biochemical studies show that p53 suppresses the rft1-1 mutation by forming a protein-protein complex with the Rft1 protein. Mutations in the gene encoding p53 have been found to be the most common genetic alterations in human cancer. p53 is thought to exert its function of tumor suppression through inhibition of cell proliferation or induction of apoptosis in response to DNA damage. Although there have been no proteins homologous to p53 identified in lower eucaryotic organisms, it is known that overexpression of wild-type human p53 can inhibit cell growth of Schizosaccharomyces pombe and Saccharomyces cerevisiae (Bischoff et al., 1992; Nigro et al., 1992), suggesting that certain aspects of p53 function may manifest or exist in yeast. In an attempt to identify the p53-like proteins in the yeast S. cerevisiae, we isolated a mutant that requires wild-type p53 for its viability. The mutant, rft1-1, is defective in cell cycle progression and arrests before mitosis when p53 protein is depleted. Genetic and biochemical studies show that p53 suppresses the rft1-1 mutation by forming a protein-protein complex with the Rft1 protein.