Altered S-AdenosylMethionine availability impacts dNTP pools in Saccharomyces cerevisiae.

IF 2.2 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yeast Pub Date : 2024-08-01 Epub Date: 2024-07-03 DOI:10.1002/yea.3973
Warunya Panmanee, Men T H Tran, Serigne N Seye, Erin D Strome
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引用次数: 0

Abstract

Saccharomyces cerevisiae has long been used as a model organism to study genome instability. The SAM1 and SAM2 genes encode AdoMet synthetases, which generate S-AdenosylMethionine (AdoMet) from Methionine (Met) and ATP. Previous work from our group has shown that deletions of the SAM1 and SAM2 genes cause changes to AdoMet levels and impact genome instability in opposite manners. AdoMet is a key product of methionine metabolism and the major methyl donor for methylation events of proteins, RNAs, small molecules, and lipids. The methyl cycle is interrelated to the folate cycle which is involved in de novo synthesis of purine and pyrimidine deoxyribonucleotides (dATP, dTTP, dCTP, and dGTP). AdoMet also plays a role in polyamine production, essential for cell growth and used in detoxification of reactive oxygen species (ROS) and maintenance of the redox status in cells. This is also impacted by the methyl cycle's role in production of glutathione, another ROS scavenger and cellular protectant. We show here that sam2∆/sam2∆ cells, previously characterized with lower levels of AdoMet and higher genome instability, have a higher level of each dNTP (except dTTP), contributing to a higher overall dNTP pool level when compared to wildtype. Unchecked, these increased levels can lead to multiple types of DNA damage which could account for the genome instability increases in these cells.

S-AdenosylMethionine 的可用性变化会影响酿酒酵母中的 dNTP 池。
长期以来,酿酒酵母一直被用作研究基因组不稳定性的模式生物。SAM1 和 SAM2 基因编码 AdoMet 合成酶,可从蛋氨酸(Met)和 ATP 生成 S-腺苷蛋氨酸(AdoMet)。我们小组以前的研究表明,SAM1 和 SAM2 基因的缺失会导致 AdoMet 水平的变化,并以相反的方式影响基因组的不稳定性。AdoMet 是蛋氨酸代谢的关键产物,也是蛋白质、RNA、小分子和脂质甲基化过程中的主要甲基供体。甲基循环与叶酸循环相互关联,叶酸循环参与嘌呤和嘧啶脱氧核苷酸(dATP、dTTP、dCTP 和 dGTP)的从头合成。AdoMet 还在多胺的产生中发挥作用,多胺是细胞生长所必需的,并用于活性氧(ROS)的解毒和维持细胞的氧化还原状态。甲基循环在生产谷胱甘肽(另一种 ROS 清除剂和细胞保护剂)中的作用也会影响这一点。我们在这里发现,与野生型细胞相比,sam2∆/sam2∆ 细胞具有较低的 AdoMet 水平和较高的基因组不稳定性,它们的每种 dNTP(dTTP 除外)水平都较高,从而导致总体 dNTP 池水平较高。如果不加以控制,这些增加的水平会导致多种类型的 DNA 损伤,这可能是这些细胞基因组不稳定性增加的原因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Yeast
Yeast 生物-生化与分子生物学
CiteScore
5.30
自引率
3.80%
发文量
55
审稿时长
3 months
期刊介绍: Yeast publishes original articles and reviews on the most significant developments of research with unicellular fungi, including innovative methods of broad applicability. It is essential reading for those wishing to keep up to date with this rapidly moving field of yeast biology. Topics covered include: biochemistry and molecular biology; biodiversity and taxonomy; biotechnology; cell and developmental biology; ecology and evolution; genetics and genomics; metabolism and physiology; pathobiology; synthetic and systems biology; tools and resources
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