DNA 的复制需要专门且复杂的机器。这种机制被称为复制体，在进化上高度保守，从简单的单细胞生物（如酵母）到人类细胞。复制体包含负责复制过程中各个步骤的多个蛋白质复合物。复制体的一个重要组成部分是 Cdc45-MCM-GINS (CMG) 解旋酶复合物，它解开双链 DNA 并协调其他复制体组件（包括 DNA 聚合酶）的组装和功能。编码 CMG 解旋酶成分的基因对于启动 DNA 复制至关重要。在这项研究中，我们旨在研究杂合酿酒酵母细胞中 CMG 复合体基因的一个副本的缺失如何影响细胞的生理和衰老。我们的数据显示，这些细胞表现出各自 CMG 解旋酶复合体蛋白转录水平的显着降低，以及细胞周期的破坏、倍增时间的延长以及生化谱的改变。值得注意的是，这项研究首次证明，编码 CMG 解旋酶亚基的基因杂合的细胞表现出显着增加的生殖潜力和延迟的衰老。此外，我们观察到酵母中 RNA 和多糖水平与其繁殖潜力之间的显着相关性，以及脂肪酸水平和细胞倍增时间之间的相关性。我们的研究结果还为酵母在研究癌症治疗潜在治疗靶点方面的潜在用途提供了新的线索。版权所有 © 2023。由 Elsevier B.V. 出版。

The replication of DNA requires specialized and intricate machinery. This machinery is known as a replisome and is highly evolutionarily conserved, from simple unicellular organisms such as yeast to human cells. The replisome comprises multiple protein complexes responsible for various steps in the replication process. One crucial component of the replisome is the Cdc45-MCM-GINS (CMG) helicase complex, which unwinds double-stranded DNA and coordinates the assembly and function of other replisome components, including DNA polymerases. The genes encoding the CMG helicase components are essential for initiating DNA replication. In this study, we aimed to investigate how the absence of one copy of the CMG complex genes in heterozygous Saccharomyces cerevisiae cells impacts the cells' physiology and aging. Our data revealed that these cells exhibited a significant reduction in transcript levels for the respective CMG helicase complex proteins, as well as disruptions in the cell cycle, extended doubling times, and alterations in their biochemical profile. Notably, this study provided the first demonstration that cells heterozygous for genes encoding subunits of the CMG helicase exhibited a significantly increased reproductive potential and delayed chronological aging. Additionally, we observed a noteworthy correlation between RNA and polysaccharide levels in yeast and their reproductive potential, as well as a correlation between fatty acid levels and cell doubling times. Our findings also shed new light on the potential utility of yeast in investigating potential therapeutic targets for cancer treatment.Copyright © 2023. Published by Elsevier B.V.