Saccharomyces cerevisiae contains two functional genes encoding 3-hydroxy-3-methylglutaryl-coenzyme A reductase.

We have isolated two genes from yeast encoding 3-hydroxy-3-methylglutaryl-coenzyme A reductase [hydroxymethylglutaryl-coenzyme A reductase (NADPH); HMG-CoA reductase; EC 1.1.1.34], the rate-limiting enzyme of sterol biosynthesis. These genes, HMG1 and HMG2, were identified by hybridization to a cDNA clone encoding hamster HMG-CoA reductase. DNA sequence analysis reveals homology between the amino ...
acid sequence of the proteins encoded by the two yeast genes and the carboxyl-terminal half of the hamster protein. Cells containing mutant alleles of both HMG1 and HMG2 are unable to undergo spore germination and vegetative growth. However, cells containing a mutant allele of either HMG1 or HMG2 are viable but are more sensitive to compactin, a competitive inhibitor of HMG-CoA reductase, than are wild-type cells. Assays of HMG-CoA reductase activity in extracts from hmg1- and hmg2- mutants indicate that HMG1 contributes at least 83% of the activity found in wild-type cells.
Mesh Terms:
Chromosome Mapping, Cloning, Molecular, Drug Resistance, Hydroxymethylglutaryl CoA Reductases, Lovastatin, Mutation, Naphthalenes, Plasmids, Saccharomyces cerevisiae, Sequence Homology, Nucleic Acid
Proc. Natl. Acad. Sci. U.S.A.
Date: Aug. 01, 1986
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