{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:44:24Z","timestamp":1792647864578,"version":"4.5.0"},"reference-count":31,"publisher":"National Academy of Sciences","issue":"44","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,11,2]]},"abstract":"<jats:p>\n                    Approximately 14% of genetic mutations in patients with ataxia-telangiectsia (A-T) are single-nucleotide changes that result in primary premature termination codons (PTCs), either UAA, UAG, or UGA. The purpose of this study was to explore a potential therapeutic approach for this subset of patients by using aminoglycosides to induce PTC read-through, thereby restoring levels of full-length ATM (A-T mutated) protein. In experiments using a modified\n                    <jats:italic>in vitro<\/jats:italic>\n                    cDNA coupled transcription\/translation protein truncation test, 13 A-T cell lines carrying PTC mutations in different contexts exhibited read-through expression of ATM fragments, with three of four aminoglycosides tested. In\n                    <jats:italic>ex vivo<\/jats:italic>\n                    experiments with lymphoblastoid cell lines, we used radiosensitivity, radioresistant DNA synthesis, and irradiation-induced autophosphorylation of ATM Ser-1981 to show that the aminoglycoside-induced full-length ATM protein was functional and corrected, to various extents, the phenotype of A-T cells. These results encourage further testing of other compounds in this class, as well as follow up animal studies. Because some A-T patients with 5\u201320% of normal levels of ATM protein show slower neurological progression, A-T may prove to be a good model for aminoglycoside-induced read-through therapy.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0405155101","type":"journal-article","created":{"date-parts":[[2004,10,21]],"date-time":"2004-10-21T20:24:05Z","timestamp":1098390245000},"page":"15676-15681","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":134,"title":["Correction of ATM gene function by aminoglycoside-induced read-through of premature termination codons"],"prefix":"10.1073","volume":"101","author":[{"given":"Chih-Hung","family":"Lai","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen H.","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shareef A.","family":"Nahas","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Midori","family":"Mitui","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin M.","family":"Gamo","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liutao","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Gatti","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,10,21]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1071-9091(03)00026-3"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01368"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.1.69"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2003.09.008"},{"key":"e_1_3_2_5_2","first-page":"93","volume":"1","year":"1965","unstructured":"Davies, J., Gorini, L. & Davis, B. 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