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DMSO has been previously observed to impair the growth of yeast cells defective in calcium movement across cellular membranes and in phosphoinositol pyrophosphate synthases. Here, we set out to investigate the Ca<jats:sup>2+<\/jats:sup>\u2010mediated response to DMSO in <jats:italic>Saccharomyces cerevisiae<\/jats:italic>. The cell exposure to DMSO was signaled by a two\u2010phase cytosolic Ca<jats:sup>2+<\/jats:sup> wave that was dependent on Mid1, a subunit of the Cch1\/Mid1 Ca<jats:sup>2+<\/jats:sup> channel located at the plasma membrane. While the vacuolar Ca<jats:sup>2+<\/jats:sup> channel Trpy1 also contributed by releasing Ca<jats:sup>2+<\/jats:sup> from the vacuole, the immediate cell response to DMSO exposure depended on the external Ca<jats:sup>2+<\/jats:sup> imported into the cell through Cch1\/Mid1. A chemogenomic screen previously performed on a collection of yeast knockout mutants identified the two phosphoinositol pyrophosphate synthases Kcs1 and Vip1 as determinants for yeast tolerance to DMSO. Deletion of <jats:italic>KCS1<\/jats:italic> or <jats:italic>VIP1<\/jats:italic> genes suppressed the DMSO\u2010induced Ca<jats:sup>2+<\/jats:sup> response, suggesting that both Ca<jats:sup>2+<\/jats:sup> and phosphoinositol pyrophosphate signaling contribute to cell adaptation under DMSO stress.<\/jats:p>","DOI":"10.1002\/2211-5463.70039","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T11:52:23Z","timestamp":1744372343000},"page":"1113-1123","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp><i>KCS1<\/i><\/scp> and <scp><i>VIP1<\/i><\/scp>, the genes encoding yeast phosphoinositol pyrophosphate synthases, are required for Ca<sup>2+<\/sup>\u2010mediated response to dimethylsulfoxide (<scp>DMSO<\/scp>)"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5361-5680","authenticated-orcid":false,"given":"Larisa 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