{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:25:07Z","timestamp":1790965507190,"version":"4.1.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,2,15]]},"abstract":"<jats:p>\n                    Spinocerebellar ataxia 10 (SCA10) is an autosomal dominant disease caused by large-scale expansions of the (ATTCT)\n                    <jats:sub>n<\/jats:sub>\n                    repeat within an intron of the human\n                    <jats:italic>ATXN10<\/jats:italic>\n                    gene. In contrast to other expandable repeats, this pentanucleotide repeat does not form stable intra- or interstranded DNA structures, being a DNA unwinding element instead. We analyzed the instability of the (ATTCT)\n                    <jats:sub>n<\/jats:sub>\n                    repeat in a yeast experimental system, where its expansions led to inactivation of the\n                    <jats:italic>URA3<\/jats:italic>\n                    reporter gene. The inactivation was due to a dramatic decrease in the mRNA levels owing to premature transcription termination and RNA polyadenylation at the repeat. The rates of expansions strongly increased with the repeat's length, mimicking genetic anticipation in human pedigrees. A first round of genetic analysis showed that a functional\n                    <jats:italic>TOF1<\/jats:italic>\n                    gene precludes, whereas a functional\n                    <jats:italic>RAD5<\/jats:italic>\n                    gene promotes, expansions of the (ATTCT)\n                    <jats:sub>n<\/jats:sub>\n                    repeat. We hypothesize that repeat expansions could occur upon fortuitous template switching during DNA replication. The rate of repeat contractions was elevated in the Tof1 knockout strain, but it was not affected by the\n                    <jats:italic>RAD5<\/jats:italic>\n                    gene. Supporting the notion of replication irregularities, we found that (ATTCT)\n                    <jats:sub>n<\/jats:sub>\n                    repeats also cause length-dependent chromosomal fragility in yeast. Repeat-mediated fragility was also affected by the Tof1 and Rad5 proteins, being reduced in their absence.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1009409108","type":"journal-article","created":{"date-parts":[[2011,1,31]],"date-time":"2011-01-31T23:07:07Z","timestamp":1296515227000},"page":"2843-2848","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":50,"title":["Expansions, contractions, and fragility of the spinocerebellar ataxia type 10 pentanucleotide repeat in yeast"],"prefix":"10.1073","volume":"108","author":[{"given":"Nicole","family":"Cherng","sequence":"first","affiliation":[{"name":"Department of Biology, Tufts University, Medford, MA 02155;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander A.","family":"Shishkin","sequence":"additional","affiliation":[{"name":"Department of Biology, Tufts University, Medford, MA 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