Chen Y, Tye B K
Section of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, New York 14853, USA.
Mol Cell Biol. 1995 Aug;15(8):4631-9. doi: 10.1128/MCB.15.8.4631.
Mcm1 is a multifunctional protein which plays a role both in the initiation of DNA replication and in the transcriptional regulation of diverse genes in Saccharomyces cerevisiae. The mcm1-1 mutation results in instability of minichromosomes and alpha-specific sterility. Second-site suppressors that restore minichromosome stability but not fertility to the mcm1-1 mutant were isolated. Two of the suppressors, pgm1-1 and pgm1-2, are mutant alleles of PGM1 which encodes a glycolytic enzyme, phosphoglycerate mutase. We show that the pgm1-1 mutation suppresses the minichromosome maintenance (Mcm) defect by increasing the protein activity or level of Mcm1-1 posttranscriptionally. This increase in the intracellular Mcm1-1 activity is sufficient to suppress the Mcm defect but only minimally suppresses the mating defect. Mutations in genes encoding other glycolytic enzymes, such as eno2::URA3, can also suppress the Mcm phenotype of mcm1-1. Suppression by these glycolytic enzyme mutations correlates with a reduced rate of glycolysis rather than a reduced rate of cell growth. This study suggests that in response to changes in their nutritional states yeast cells may attain homeostasis by modulating the activity of global regulators like Mcm1, which plays a central role in the regulation of energy-expensive anabolic processes.
Mcm1是一种多功能蛋白，在酿酒酵母中，它在DNA复制起始以及多种基因的转录调控过程中均发挥作用。mcm1 - 1突变会导致微型染色体不稳定以及α因子特异性不育。我们分离出了能恢复mcm1 - 1突变体微型染色体稳定性但不能恢复育性的第二位点抑制子。其中两个抑制子pgm1 - 1和pgm1 - 2是PGM1的突变等位基因，PGM1编码一种糖酵解酶——磷酸甘油酸变位酶。我们发现pgm1 - 1突变通过转录后增加Mcm1 - 1的蛋白活性或水平来抑制微型染色体维持（Mcm）缺陷。细胞内Mcm1 - 1活性的这种增加足以抑制Mcm缺陷，但只能最小程度地抑制交配缺陷。编码其他糖酵解酶的基因发生突变，如eno2::URA3，也能抑制mcm1 - 1的Mcm表型。这些糖酵解酶突变引起的抑制作用与糖酵解速率降低相关，而非细胞生长速率降低。这项研究表明，响应营养状态的变化，酵母细胞可能通过调节像Mcm1这样在能量消耗大的合成代谢过程调控中起核心作用的全局调节因子的活性来实现稳态。
