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Cell and Organelle Structure and Assembly

The Yeast Gene ERG6 Is Required for Normal Membrane Function but Is Not Essential for Biosynthesis of the Cell-Cycle-Sparking Sterol

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Pages 3447-3456 | Received 19 Jan 1989, Accepted 11 May 1989, Published online: 31 Mar 2023
 

Abstract

In Saccharomyces cerevisiae, methylation of the principal membrane sterol at C-24 produces the C-28 methyl group specific to ergosterol and represents one of the few structural differences between ergosterol and cholesterol. C-28 in S. cerevisiae has been suggested to be essential for the sparking function (W. J. Pinto and W. R. Nes, J. Biol. Chem. 258:4472-4476, 1983), a cell cycle event that may be required to enter Gl (C. Dahl, H.-P. Biemann, and J. Dahl, Proc. Natl. Acad. Sci. USA 84:4012-4016,1987). The sterol biosynthetic pathway in 5. cerevisiae was genetically altered to assess the functional role of the C-28 methyl group of ergosterol. ERG6, the putative structural gene for S-adenosylmethionine:Δ24-methyltransferase, which catalyzes C-24 methylation, was cloned, and haploid strains containing erg6 null alleles (erg6Δ1 and erg6Δ::LEU2) were generated. Although erg6Δ cells are unable to methylate ergosterol precursors at C-24, they exhibit normal vegetative growth, suggesting that C-28 sterols are not essential in S. cerevisiae. However, erg6Δ cells exhibit pleiotropic phenotypes that include defective conjugation, hypersensitivity to cycloheximide, resistance to nystatin, a severely diminished capacity for genetic transformation, and defective tryptophan uptake. These phenotypes reflect the role of ergosterol as a regulator of membrane permeability and fluidity. Genetic mapping experiments revealed that ERG6 is located on chromosome XIII, tightly linked to sec59.

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