THE YEAST GENE ERG6 IS REQUIRED FOR NORMAL MEMBRANE-FUNCTION BUT IS NOT ESSENTIAL FOR BIOSYNTHESIS OF THE CELL-CYCLE-SPARKING STEROL
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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DOI：
10.1128/mcb.9.8.3447
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发表时间：
1989-08-01
影响因子：
5.3
通讯作者：
BARD, M
中科院分区：
文献类型：
--
作者：
GABER, RF;COPPLE, DM;BARD, M
在酿酒酵母中，主要膜甾醇在C - 24位的甲基化产生了麦角甾醇特有的C - 28甲基，这是麦角甾醇和胆固醇之间为数不多的结构差异之一。酿酒酵母中的C - 28已被认为对激发功能至关重要（W. J. 平托和W. R. 内斯，《生物化学杂志》258:4472 - 4476，1983年），激发功能是一种细胞周期事件，可能是进入G1期所必需的（C. 达尔、H. - P. 比曼和J. 达尔，《美国国家科学院院刊》84:4012 - 4016，1987年）。对酿酒酵母中的甾醇生物合成途径进行了基因改造，以评估麦角甾醇C - 28甲基的功能作用。ERG6是S - 腺苷甲硫氨酸：Δ24 - 甲基转移酶的推定结构基因，该酶催化C - 24甲基化，ERG6被克隆，并且产生了含有erg6无效等位基因（erg6Δ1和erg6Δ::LEU2）的单倍体菌株。尽管erg6Δ细胞无法在C - 24位对麦角甾醇前体进行甲基化，但它们表现出正常的营养生长，这表明C - 28甾醇在酿酒酵母中不是必需的。然而，erg6Δ细胞表现出多效性表型，包括接合缺陷、对环己酰亚胺高度敏感、对制霉菌素具有抗性、遗传转化能力严重降低以及色氨酸摄取缺陷。这些表型反映了麦角甾醇作为膜通透性和流动性调节剂的作用。遗传作图实验表明，ERG6位于第十三号染色体上，与sec59紧密连锁。
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 G1 (C. Dahl, H.-P. Biemann, and J. Dahl, Proc. Natl. Acad. Sci. USA 84:4012-4016, 1987). The sterol biosynthetic pathway in S. 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:.DELTA.24-methyltransferase, which catalyzes C-24 methylation, was cloned, and haploid strains containing erg6 null alleles (erg6.DELTA.1 and erg6.DELTA.::LEU2) were generated. Although erg6.DELTA. 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, erg6.DELTA. 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.