{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:17:31Z","timestamp":1791919051542,"version":"4.3.4"},"reference-count":58,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2016,9,27]],"date-time":"2016-09-27T00:00:00Z","timestamp":1474934400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,11,2]],"date-time":"2016-11-02T00:00:00Z","timestamp":1478044800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["2R01 NS046478"],"award-info":[{"award-number":["2R01 NS046478"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM099774"],"award-info":[{"award-number":["R01GM099774"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2016,11,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Proteins containing polyglutamine (polyQ) regions are found in almost all eukaryotes, albeit with various frequencies. In humans, proteins such as huntingtin (Htt) with abnormally expanded polyQ regions cause neurodegenerative diseases such as Huntington\u2019s disease (HD). To study how the presence of endogenous polyQ aggregation modulates polyQ aggregation and toxicity, we expressed polyQ expanded Htt fragments (polyQ Htt) in\n            <jats:named-content content-type=\"genus-species\">Schizosaccharomyces pombe<\/jats:named-content>\n            . In stark contrast to other unicellular fungi, such as\n            <jats:named-content content-type=\"genus-species\">Saccharomyces cerevisiae<\/jats:named-content>\n            ,\n            <jats:named-content content-type=\"genus-species\">S. pombe<\/jats:named-content>\n            is uniquely devoid of proteins with more than 10 Q repeats. We found that polyQ Htt forms aggregates within\n            <jats:named-content content-type=\"genus-species\">S. pombe<\/jats:named-content>\n            cells only with exceedingly long polyQ expansions. Surprisingly, despite the presence of polyQ Htt aggregates in both the cytoplasm and nucleus, no significant growth defect was observed in\n            <jats:named-content content-type=\"genus-species\">S. pombe<\/jats:named-content>\n            cells. Further, PCR analysis showed that the repetitive polyQ-encoding DNA region remained constant following transformation and after multiple divisions in\n            <jats:named-content content-type=\"genus-species\">S. pombe<\/jats:named-content>\n            , in contrast to the genetic instability of polyQ DNA sequences in other organisms. These results demonstrate that cells with a low content of polyQ or other aggregation-prone proteins can show a striking resilience with respect to polyQ toxicity and that genetic instability of repetitive DNA sequences may have played an important role in the evolutionary emergence and exclusion of polyQ expansion proteins in different organisms.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Polyglutamine (polyQ) proteins encoded by repetitive CAG DNA sequences serve a variety of normal biological functions. Yet some proteins with abnormally expanded polyQ regions cause neurodegeneration through unknown mechanisms. To study how distinct cellular environments modulate polyQ aggregation and toxicity, we expressed CAG-expanded huntingtin fragments in\n            <jats:named-content content-type=\"genus-species\">Schizosaccharomyces pombe<\/jats:named-content>\n            . In stark contrast to many other eukaryotes,\n            <jats:named-content content-type=\"genus-species\">S. pombe<\/jats:named-content>\n            is uniquely devoid of proteins containing long polyQ tracts. Our results show that\n            <jats:named-content content-type=\"genus-species\">S. pombe<\/jats:named-content>\n            cells, despite their low content of endogenous polyQ proteins, exhibit striking and unexpected resilience with respect to polyQ toxicity and that genetic instability of repetitive DNA sequences may have played an important role in the emergence and expansion of polyQ domains in eukaryotic evolution.\n          <\/jats:p>","DOI":"10.1128\/mbio.01367-16","type":"journal-article","created":{"date-parts":[[2016,9,28]],"date-time":"2016-09-28T01:20:06Z","timestamp":1475025606000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["CAG Expansions Are Genetically Stable and Form Nontoxic Aggregates in Cells Lacking Endogenous Polyglutamine Proteins"],"prefix":"10.1128","volume":"7","author":[{"given":"Ashley A.","family":"Zurawel","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Kabeche","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja E.","family":"DiGregorio","sequence":"additional","affiliation":[{"name":"Department of Pathology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kartikeya M.","family":"Menon","sequence":"additional","affiliation":[{"name":"Department of 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