{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T23:04:09Z","timestamp":1774047849853,"version":"3.50.1"},"reference-count":46,"publisher":"Proceedings of the National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,12,18]]},"abstract":"<jats:p>\n            Sir2p is an NAD\n            <jats:sup>+<\/jats:sup>\n            -dependent histone deacetylase\n required for chromatin-dependent silencing in yeast. In a cell-based\n screen for inhibitors of Sir2p, we identified a compound, splitomicin,\n that creates a conditional phenocopy of a\n            <jats:italic>sir2<\/jats:italic>\n            deletion mutant in\n            <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n            . Cells grown\n in the presence of the drug have silencing defects at telomeres, silent\n mating-type loci, and the ribosomal DNA. In addition, whole genome\n microarray experiments show that splitomicin selectively inhibits\n Sir2p.\n            <jats:italic>In vitro<\/jats:italic>\n            , splitomicin inhibits\n NAD\n            <jats:sup>+<\/jats:sup>\n            -dependent histone deacetylase activity (HDA) of the\n Sir2 protein. Mutations in\n            <jats:italic>SIR2<\/jats:italic>\n            that confer\n resistance to the drug map to the likely acetylated histone tail\n binding domain of the protein. By using splitomicin as a chemical\n genetic probe, we demonstrate that continuous HDA of Sir2p is required\n for maintaining a silenced state in nondividing cells.\n          <\/jats:p>","DOI":"10.1073\/pnas.261574398","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:36:44Z","timestamp":1027694204000},"page":"15113-15118","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":292,"title":["Identification of a small molecule inhibitor of Sir2p"],"prefix":"10.1073","volume":"98","author":[{"given":"Antonio","family":"Bedalov","sequence":"first","affiliation":[{"name":"Divisions of Clinical Research, Basic Sciences, and\r Human Biology, Fred Hutchinson Cancer Research Center,\r 1100 Fairview Avenue North, Seattle, WA 98109"}]},{"given":"Tonibelle","family":"Gatbonton","sequence":"additional","affiliation":[{"name":"Divisions of Clinical Research, Basic Sciences, and\r Human Biology, Fred Hutchinson Cancer Research Center,\r 1100 Fairview Avenue North, Seattle, WA 98109"}]},{"given":"William P.","family":"Irvine","sequence":"additional","affiliation":[{"name":"Divisions of Clinical Research, Basic Sciences, and\r Human Biology, Fred Hutchinson Cancer Research Center,\r 1100 Fairview Avenue North, Seattle, WA 98109"}]},{"given":"Daniel E.","family":"Gottschling","sequence":"additional","affiliation":[{"name":"Divisions of Clinical Research, Basic Sciences, and\r Human Biology, Fred Hutchinson Cancer Research Center,\r 1100 Fairview Avenue North, Seattle, WA 98109"}]},{"given":"Julian A.","family":"Simon","sequence":"additional","affiliation":[{"name":"Divisions of Clinical Research, Basic Sciences, and\r Human Biology, Fred Hutchinson Cancer Research Center,\r 1100 Fairview Avenue North, Seattle, WA 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