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U.S.A."],"published-print":{"date-parts":[[2020,4,7]]},"abstract":"<jats:title>Significance<\/jats:title>\n          <jats:p>\n            Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease with no effective treatments. SCA3 is etiologically linked to an abnormal polyglutamine (polyQ) tract at the C terminus of Ataxin-3 (ATXN3). How this polyQ stretch causes SCA3 pathology remains elusive. Here we provide evidence that wild-type ATXN3 plays an important role in error-free repair of DNA double-strand breaks in the transcribed genes. In contrast, mutant ATXN3 blocks the activity of a DNA end-processing enzyme, polynucleotide kinase 3\u2032-phosphatase (PNKP), leading to progressive accumulation of double-strand breaks and abrogation of global transcription. Since PNKP overexpression in\n            <jats:italic>Drosophila<\/jats:italic>\n            rescued the SCA3 phenotype, this promising therapeutic avenue for SCA3 is worth exploring.\n          <\/jats:p>","DOI":"10.1073\/pnas.1917280117","type":"journal-article","created":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T00:21:06Z","timestamp":1585009266000},"page":"8154-8165","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":38,"title":["Deficiency in classical nonhomologous end-joining\u2013mediated repair of transcribed genes is linked to SCA3 pathogenesis"],"prefix":"10.1073","volume":"117","author":[{"given":"Anirban","family":"Chakraborty","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of Texas Medical Branch, Galveston, TX 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