{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:58:44Z","timestamp":1790841524076,"version":"4.1.0"},"reference-count":0,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Institute of General Medical Sciences","award":["GM112793"],"award-info":[{"award-number":["GM112793"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of General Medical Sciences","award":["GM112793"],"award-info":[{"award-number":["GM112793"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of General Medical Sciences","award":["GM130858"],"award-info":[{"award-number":["GM130858"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of General Medical Sciences","award":["P20GM103418"],"award-info":[{"award-number":["P20GM103418"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Cancer Center, University of Kansas","award":["1003863 KAN"],"award-info":[{"award-number":["1003863 KAN"]}],"id":[{"id":"https:\/\/ror.org\/001tmjg57","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Office of Research, University of Kansas","award":["1003391"],"award-info":[{"award-number":["1003391"]}],"id":[{"id":"https:\/\/ror.org\/001tmjg57","id-type":"ROR","asserted-by":"crossref"}]},{"name":"University of Kansas","award":["2144083"],"award-info":[{"award-number":["2144083"]}],"id":[{"id":"https:\/\/ror.org\/001tmjg57","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Japan Society for the Promotion of Science","award":["JP22K19466"],"award-info":[{"award-number":["JP22K19466"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Japan Society for the Promotion of Science","award":["JP23H00411"],"award-info":[{"award-number":["JP23H00411"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Japan Society for the Promotion of Science","award":["JP24H01382"],"award-info":[{"award-number":["JP24H01382"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Takeda Science Foundation","id":[{"id":"https:\/\/ror.org\/02y123g31","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Mitotic functions of Topoisomerase II\u03b1 (TopoII\u03b1) are dictated by its C-terminal domain (CTD), which is distinct from TopoII\u03b2. The chromatin-tether domain (ChT) within the \u03b1CTD recognizes methylated chromatin, an ability lacking for TopoII\u03b2 and loss of \u03b1ChT leads to ultrafine DNA bridges (UFBs) and chromosome bridges in anaphase. Because UFBs arise from incomplete decatenation of tangled genomic DNA, these observations suggest that \u03b1ChT directs TopoII\u03b1 to sites of tangled DNA. Here, by chimeric swapping of ChT domains between the isoforms, TopoII\u03b1-\u03b2ChT and TopoII\u03b2-\u03b1ChT, we reveal that \u03b1ChT improves TopoII\u03b2\u2018s ability for UFB resolution but not for preventing chromosome bridges. This highlights the requirement for a complete \u03b1CTD for accurate chromosome segregation. Salt extraction assays show that the full \u03b1CTD is required for stable TopoII\u03b1 association with mitotic chromosomes, while the \u03b1ChT enhances this association without affecting decatenation activity. Moreover, proteomic analysis showed altered levels of condensin and centromeric proteins in TopoII mutants. These results reveal the role of \u03b1ChT in the \u03b1CTD-dependent chromosomal targeting mechanism of TopoII\u03b1 as well as an \u03b1ChT-dependent requirement for robust structural organization of mitotic chromosomes.<\/jats:p>","DOI":"10.1242\/jcs.264838","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:16:41Z","timestamp":1790839001000},"source":"Crossref","is-referenced-by-count":0,"title":["Contribution of Topoisomerase II\u03b1 chromatin-tether and C-terminal domain to mitotic chromosome association and structural organization"],"prefix":"10.1242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5275-7230","authenticated-orcid":false,"given":"Bunu","family":"Lama","sequence":"first","affiliation":[{"name":"1 Department of Molecular Biosciences, University of Kansas, Lawrence, KS, 66045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9078-9441","authenticated-orcid":false,"given":"Sanjana","family":"Sundararajan","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Biosciences, University of Kansas, Lawrence, KS, 66045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6756-0975","authenticated-orcid":false,"given":"Anita","family":"Saraf","sequence":"additional","affiliation":[{"name":"2 Mass Spectrometry & Analytical Proteomics Laboratory, University of Kansas, Lawrence, KS,66047, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyewon","family":"Park","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Biosciences, University of Kansas, Lawrence, KS, 66045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asbin","family":"Chand","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Biosciences, University of Kansas, Lawrence, KS, 66045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regan","family":"Krueger","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Biosciences, University of Kansas, Lawrence, KS, 66045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Saito-Fujita","sequence":"additional","affiliation":[{"name":"3 Division of Cancer Biology, The Cancer Institute of Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2601-2806","authenticated-orcid":false,"given":"Noriko","family":"Saitoh","sequence":"additional","affiliation":[{"name":"3 Division of Cancer Biology, The Cancer Institute of Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Kawano","sequence":"additional","affiliation":[{"name":"4 Department of Bioscience, Faculty of Life Science, Okayama University of Science, Okayama 700-0081, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7795-3294","authenticated-orcid":false,"given":"Duncan J.","family":"Clarke","sequence":"additional","affiliation":[{"name":"5 Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9634-6676","authenticated-orcid":false,"given":"Yoshiaki","family":"Azuma","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Biosciences, University of Kansas, Lawrence, KS, 66045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,10,1]]},"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.264838\/3719914\/jcs264838.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.264838\/3719914\/jcs264838.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:16:42Z","timestamp":1790839002000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/doi\/10.1242\/jcs.264838\/373060\/Contribution-of-Topoisomerase-II-chromatin-tether"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1242\/jcs.264838","relation":{},"ISSN":["0021-9533","1477-9137"],"issn-type":[{"value":"0021-9533","type":"print"},{"value":"1477-9137","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]},"article-number":"jcs.264838"}}