| http://purl.uniprot.org/citations/32205441 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32205441 | http://www.w3.org/2000/01/rdf-schema#comment | "Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative disease caused by CAG (encoding glutamine) repeat expansion in the Ataxin-3 (ATXN3) gene. We have shown previously that ATXN3-depleted or pathogenic ATXN3-expressing cells abrogate polynucleotide kinase 3'-phosphatase (PNKP) activity. Here, we report that ATXN3 associates with RNA polymerase II (RNAP II) and the classical nonhomologous end-joining (C-NHEJ) proteins, including PNKP, along with nascent RNAs under physiological conditions. Notably, ATXN3 depletion significantly decreased global transcription, repair of transcribed genes, and error-free double-strand break repair of a 3'-phosphate-containing terminally gapped, linearized reporter plasmid. The missing sequence at the terminal break site was restored in the recircularized plasmid in control cells by using the endogenous homologous transcript as a template, indicating ATXN3's role in PNKP-mediated error-free C-NHEJ. Furthermore, brain extracts from SCA3 patients and mice show significantly lower PNKP activity, elevated p53BP1 level, more abundant strand-breaks in the transcribed genes, and degradation of RNAP II relative to controls. A similar RNAP II degradation is also evident in mutant ATXN3-expressing Drosophila larval brains and eyes. Importantly, SCA3 phenotype in Drosophila was completely amenable to PNKP complementation. Hence, salvaging PNKP's activity can be a promising therapeutic strategy for SCA3."xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1917280117"xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/author | "Chen X."xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/author | "Chakraborty A."xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/author | "Hazra T.K."xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/author | "Ghosh G."xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/author | "Sarker A.H."xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/author | "Ashizawa T."xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/author | "Maciel P."xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/author | "Vasquez V."xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/author | "Hegde M.L."xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/author | "Mitra J."xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/author | "Huai W."xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/author | "Venkova T."xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/author | "Sarkar P.S."xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/author | "Tapryal N."xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/author | "Duarte-Silva S."xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/pages | "8154-8165"xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/title | "Deficiency in classical nonhomologous end-joining-mediated repair of transcribed genes is linked to SCA3 pathogenesis."xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://purl.uniprot.org/core/volume | "117"xsd:string |
| http://purl.uniprot.org/citations/32205441 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/32205441 |
| http://purl.uniprot.org/citations/32205441 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/32205441 |