{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T21:49:20Z","timestamp":1790545760841,"version":"4.1.0"},"reference-count":70,"publisher":"National Academy of Sciences","issue":"4","license":[{"start":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T00:00:00Z","timestamp":1642464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,1,25]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Ataxia with oculomotor apraxia (AOA) is a progressive neurodegenerative disease characterized by early\u2010onset autosomal recessive cerebellar ataxia with oculomotor apraxia, peripheral axonal neuropathy, and impaired motor functions. The AOA-2 subgroup results from mutations in an RNA\/DNA helicase, Senataxin, which is encoded by the\n                    <jats:italic>SETX<\/jats:italic>\n                    gene. Here, we carried out integrated genome and transcriptome analyses of cell lines derived from individuals with AOA2, as well as CRISPR\/Cas9 generated\n                    <jats:italic>SETX<\/jats:italic>\n                    knockouts, and observed genome-wide chromosome fragility. Genome instability was caused by increased transcription stress and the accumulation of RNA\/DNA hybrids near gene promotors, resulting in aberrant DNA repair that led to changes in gene-expression profiles. The results indicate that\n                    <jats:italic>SETX<\/jats:italic>\n                    -defective cells exhibit transcription stress that leads to chromosome fragility.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2114314119","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T17:56:03Z","timestamp":1642528563000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":31,"title":["Integrated genome and transcriptome analyses reveal the mechanism of genome instability in ataxia with oculomotor apraxia 2"],"prefix":"10.1073","volume":"119","author":[{"given":"Radhakrishnan","family":"Kanagaraj","sequence":"first","affiliation":[{"name":"DNA Recombination and Repair Laboratory, The Francis Crick Institute, London NW1 1AT, United 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