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- W2964276475 abstract "Maintenance of genome integrity is a crucial cellular focus that involves a wide variety of proteins functioning in multiple processes. Defects in many different pathways can result in genome instability, a hallmark of cancer. Utilizing a diploid Saccharomyces cerevisiae model, we previously reported a collection of gene mutations that affect genome stability in a haploinsufficient state. In this work we explore the effect of gene dosage on genome instability for one of these genes and its paralog; SAM1 and SAM2 These genes encode S-Adenosylmethionine (AdoMet) synthetases, responsible for the creation of AdoMet from methionine and ATP. AdoMet is the universal methyl donor for methylation reactions and is essential for cell viability. It is the second most used cellular enzyme substrate and is exceptionally well-conserved through evolution. Mammalian cells express three genes, MAT1A, MAT2A, and MAT2B, with distinct expression profiles and functions. Alterations to these AdoMet synthetase genes, and AdoMet levels, are found in many cancers, making them a popular target for therapeutic intervention. However, significant variance in these alterations are found in different tumor types, with the cellular consequences of the variation still unknown. By studying this pathway in the yeast system, we demonstrate that losses of SAM1 and SAM2 have different effects on genome stability through distinctive effects on gene expression and AdoMet levels, and ultimately separate effects on the methyl cycle. Thus, this study provides insight into the mechanisms by which differential expression of the SAM genes have cellular consequences that affect genome instability." @default.
- W2964276475 created "2019-07-30" @default.
- W2964276475 creator A5000213505 @default.
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- W2964276475 creator A5077767873 @default.
- W2964276475 date "2019-09-01" @default.
- W2964276475 modified "2023-10-14" @default.
- W2964276475 title "Mutations in the S-Adenosylmethionine Synthetase Genes <i>SAM1</i> and <i>SAM2</i> Differentially Affect Genome Stability in <i>Saccharomyces cerevisiae</i>" @default.
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- W2964276475 doi "https://doi.org/10.1534/genetics.119.302435" @default.
- W2964276475 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6727793" @default.
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- W2964276475 hasPublicationYear "2019" @default.
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