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Vulnerable Nucleotide Pools and Genomic Instability in Yeast Strains with Deletion of the ADE12 Gene Encoding for Adenylosuccinate Synthetase
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Vulnerable Nucleotide Pools and Genomic Instability in Yeast Strains with Deletion of the ADE12 Gene Encoding for Adenylosuccinate Synthetase
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Journal Article
Vulnerable Nucleotide Pools and Genomic Instability in Yeast Strains with Deletion of the ADE12 Gene Encoding for Adenylosuccinate Synthetase
2025
Overview
Adenylosuccinate synthetase (AdSS), encoded by the ADE12 gene in yeast Saccharomyces cerevisiae, plays a critical role in purine biosynthesis, catalyzing the conversion of inosine 5′-monophosphate (IMP) and aspartic acid to adenylosuccinate, a substrate for the following adenosine 5′-monophosphate (AMP) synthesis step. Mutants lacking AdSS activity exhibit a range of pleiotropic phenotypes: slow growth, poor spore germination, accumulation, and secretion of inosine and hypoxanthine. We report new phenotypes of ade12 mutants and explain their molecular mechanisms. A GC-MS analysis showed that ade12 mutants have highly altered metabolite profiles: the accumulation of IMP leads to an impaired cellular energy metabolism, resulting in a dysregulation of key processes—the metabolism of nucleotides, carbohydrates, and amino acids. These metabolic perturbations explain the cell division arrest observed in ade12 yeast strains. A slowed replication in ade12 mutants, because of the insufficient availability of energy, nucleotides, and proteins, leads to the error-prone DNA polymerase ζ-dependent elevation of spontaneous mutagenesis, connecting multiple roles of AdSS in metabolism with genome stability control.
Publisher
MDPI AG,MDPI
Subject
/ Adenylosuccinate Synthase - genetics
/ Adenylosuccinate Synthase - metabolism
/ Analysis
/ Enzymes
/ Genes
/ Ligases
/ Mutation
/ Purines
/ Saccharomyces cerevisiae - genetics
/ Saccharomyces cerevisiae - metabolism
/ Saccharomyces cerevisiae Proteins - genetics
/ Saccharomyces cerevisiae Proteins - metabolism
/ Yeast
