YEAST GROWTH-CONTROL GENE GRC5 IS HIGHLY HOMOLOGOUS TO THE MAMMALIAN PUTATIVE TUMOR-SUPPRESSOR GENE QM

We isolated the Saccharomyces cerevisiae GRC5 (growth control) gene by functional complementation in vivo of a ts (temperature sensitive) mu tation. Phenotypic analysis suggested involvement of GRC5 in cell grow th and proliferation. Mutant cells arrest their cell cycles after one to three cell divisions predominantly as mother cells with a large bud . In the region of the septum, a massive accumulation of cell wall mat erial is observed. The mother and daughter nuclei are well separated a nd spindles are no longer present, while the cytoskeleton is of aberra nt appearance. Arrested cells do not perform protein synthesis and are unable to mate. Furthermore, grc5-1(ts) cells rapidly lose viability at the restrictive temperature (37 degrees C) only on full media, but not under nitrogen-starvation conditions, indicating that proper respo nse to this nutrient limitation is still intact in mutant cells after cell cycle arrest. The sequence of GRC5 translates into a basic protei n of 221 amino acids with a corresponding M(r) of 25.4 kDa. GRC5 is a member of the highly conserved QM gene family, members of which have b een reported from plants, invertebrates and vertebrates. The amino aci d sequence of GRC5 over its entire length is more than 60% identical t o the human QM protein, expression of which is associated with loss of the tumorigenic phenotype in a cell line derived from Wilms' tumor, a malignancy of the embyronic kidney. Here, we show that GRC5 is an ess ential yeast gene, the function of which as inferred from analysis of the grc5-1(ts) mutant is crucial for establishment of proper cytoskele tal structure and regulation of growth in yeast cells.