{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:04:05Z","timestamp":1791317045440,"version":"4.3.1"},"reference-count":31,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5820","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2007,3,30]]},"abstract":"<jats:p>\n                    Although expansion of trinucleotide repeats accounts for over 30 human diseases, mechanisms of repeat instability remain poorly understood. We show that a\n                    <jats:italic>Drosophila<\/jats:italic>\n                    model for the CAG\/polyglutamine (polyQ) disease spinocerebellar ataxia type 3 recapitulates key features of human CAG-repeat instability, including large repeat changes and strong expansion bias. Instability is dramatically enhanced by transcription and modulated by nuclear excision repair and a regulator of DNA repair adenosine 3\u2032,5\u2032-monophosphate (cAMP) response element\u2013binding protein (CREB)\u2013binding protein\u2014a histone acetyltransferase (HAT) whose decreased activity contributes to polyQ disease. Pharmacological treatment to normalize acetylation suppressed instability. Thus, toxic consequences of pathogenic polyQ protein may include enhancing repeat instability.\n                  <\/jats:p>","DOI":"10.1126\/science.1139517","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T23:17:19Z","timestamp":1172791039000},"page":"1857-1859","source":"Crossref","is-referenced-by-count":123,"title":["CREB-Binding Protein Modulates Repeat Instability in a\n                    <i>Drosophila<\/i>\n                    Model for PolyQ Disease"],"prefix":"10.1126","volume":"315","author":[{"given":"Joonil","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Biology, University of Pennsylvania, Philadelphila, PA 19104, USA."},{"name":"Howard Hughes Medical Institute, University of Pennsylvania, Philadelphila, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Bonini","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pennsylvania, Philadelphila, PA 19104, USA."},{"name":"Howard Hughes Medical Institute, University of Pennsylvania, Philadelphila, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1691"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1689"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0297-197"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81200-3"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200264"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2004.12.008"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1194-221"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/302578"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.7.791"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.7.1063"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.1.115"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.1.99"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.12.2135"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki697"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/70598"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg202"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb1042"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-002-0341-7"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00453-7"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1056784"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.152101299"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg002"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2004.06.029"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1087503"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/35099568"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867033456530"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00533-6"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg352"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5334.1990"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.310.5745.43"},{"key":"e_1_3_1_32_2","unstructured":"We thank R. Pittman H. Paulson A. Cashmore D. Lessing L. Li M. Watson for comments; S. DiNardo L. Thompson L. Goldstein and P. Jin for reagents; and K. Xu and X. Teng for technical assistance. Supported by grants from the Hereditary Disease Foundation (to J.J.) the Packard Foundation and NINDS (to N.M.B.). N.M.B. is an investigator of the Howard Hughes Medical Institute."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1139517","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T03:14:40Z","timestamp":1704856480000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1139517"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,3,30]]},"references-count":31,"journal-issue":{"issue":"5820","published-print":{"date-parts":[[2007,3,30]]}},"alternative-id":["10.1126\/science.1139517"],"URL":"https:\/\/doi.org\/10.1126\/science.1139517","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1070725.524625","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1070725.543401","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1070725.531697","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,3,30]]}}}