SUPPRESSION OF THE YEAST MUTATION RFT1-1 BY HUMAN P53

Mutations in the gene encoding p53 have been found to be the most comm on genetic alterations in human cancer. p53 is thought to exert its fu nction of tumor suppression through inhibition of cell proliferation o r induction of apoptosis in response to DNA damage. Although there hav e been no proteins homologous to p53 identified in lower eucaryotic or ganisms, it is known that overexpression of mild-type human p53 can in hibit cell growth of Schizosaccharomyces pombe and Saccharomyces cerev isiae (Bischoff et al., 1992; Nigro et al., 1992), suggesting that cer tain aspects of p53 function may manifest or exist in yeast. In an att empt to identify the p53-like proteins in the yeast S. cerevisiae, we isolated a mutant that requires wild-type p53 for its viability. The m utant, rft1-1, is defective in cell cycle progression and arrests befo re mitosis when p53 protein is depleted. Genetic and biochemical studi es show that p53 suppresses the rft1-1 mutation by forming a protein-p rotein complex with the Rft1 protein.