Project: Research project

Project Details


There are two genes, RAS1 and RAS2, in the yeast Saccharomyces cerevisiae
that share extensive homology with each other and with the human
proto-oncogene family c-ras. We will conduct a genetic and physiologic
study of the yeast RAS1 and RAS2 genes in order to determine the role these
genes play in the normal growth of a single eucaryotic cell. It is
anticipated that results from these studies will yeild insight into the
role c-ras genes play in higher eucaryotic cells and suggest some
mechanisms by which single amino acid changes in those genes can result in
proliferative transformation.

In preliminary studies we have defined a number of phenotypes associated
with specific mutant alleles of RAS1 and RAS2. Strains lacking both RAS
genes (ras1[unreadable]-[unreadable] ras2[unreadable]-[unreadable]) are nonviable. Strains containing mutant RAS
alleles consisting of single amino acid mutations analogous to the
transformation-activating alleles of human c-ras are viable. However, they
show a number of altered phenotypes: they display a dominant deficiency in
sporulation (Spo[unreadable]-[unreadable]); they fail to arrest uniformly at the beginning of the
cell cycle when starved for various nutrients; they show a substantial
reduction in viability upon starvation; and, they fail to accumulate
glycogen and trehalose. Finally, increased expression of these mutant
alleles causes lethality.

We plan to assess the interrelations between the RAS system and
cAMP-mediated growth regulation through specific constructions and genetic
physiological studies. We will evaluate the structure and functions of
RAS1 through identification and characterization of ts-lethal and Spo[unreadable]-[unreadable]
alleles of the gene following site-directed mutagenesis. We will define
those components that physically interact with the RAS proteins through
biochemical cross-linking studies and through isolation of allele-specific
suppressors of various RAS mutations. Finally, we hope to identify both
additional components of the RAS system and possible alternative regulatory
pathways by isolating and characterizing allele-non-specific suppressors of
various RAS mutants. (X)
Effective start/end date12/31/8912/31/89


  • National Cancer Institute


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