<title>Abstract</title>Cellular metabolism is directly or indirectly associated with various cellular processes by producing a variety of metabolites. Metabolic alterations may cause adverse effects on cell viability. However, some alterations potentiate the rescue of the malfunction of the cell system. Here, we found that the alteration of glucose metabolism suppressed genome instability caused by the impairment of chromatin structure. Deletion of the <italic>TDH2</italic> gene, which encodes glyceraldehyde 3-phospho dehydrogenase and is essential for glycolysis/gluconeogenesis, partially suppressed DNA damage sensitivity due to chromatin structure, which was persistently acetylated histone H3 on lysine 56 in cells with deletions of both <italic>HST3</italic> and <italic>HST4,</italic> encoding NAD⁺-dependent deacetylases. <italic>tdh2</italic> deletion also restored the short replicative lifespan of cells with deletion of <italic>sir2</italic>, another NAD⁺-dependent deacetylase, by suppressing intrachromosomal recombination in rDNA repeats increased by the unacetylated histone H4 on lysine 16. <italic>tdh2</italic> deletion also suppressed recombination between direct repeats in <italic>hst3</italic>∆ <italic>hst4</italic>∆ cells by suppressing the replication fork instability that leads to both DNA deletions among repeats. We focused on quinolinic acid (QUIN), a metabolic intermediate in the de novo nicotinamide adenine dinucleotide (NAD⁺) synthesis pathway, which accumulated in the <italic>tdh2</italic> deletion cells and was a candidate metabolite to suppress DNA replication fork instability. Deletion of <italic>QPT1</italic>, quinolinate phosphoribosyl transferase, elevated intracellular QUIN levels and partially suppressed the DNA damage sensitivity of <italic>hst3</italic>∆ <italic>hst4</italic>∆ cells as well as <italic>tdh2</italic>∆ cells. <italic>qpt1</italic> deletion restored the short replicative lifespan of <italic>sir2</italic>∆ cells by suppressing intrachromosomal recombination among rDNA repeats. In addition, <italic>qpt1</italic> deletion could suppress replication fork slippage between direct repeats. These findings suggest a connection between glucose metabolism and genomic stability.