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Chromosome mis-segregation and cytokinesis failure in trisomic human cells

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dc.contributor.authorNicholson, Joshua M.en
dc.contributor.authorMacedo, Joana C.en
dc.contributor.authorMattingly, Aaron J.en
dc.contributor.authorWangsa, Darawaleeen
dc.contributor.authorCamps, Jordien
dc.contributor.authorLima, Veraen
dc.contributor.authorGomes, Ana M.en
dc.contributor.authorDoria, Sofiaen
dc.contributor.authorRied, Thomasen
dc.contributor.authorLogarinho, Elsaen
dc.contributor.authorCimini, Danielaen
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.date.accessioned2018-08-28T14:18:18Zen
dc.date.available2018-08-28T14:18:18Zen
dc.date.issued2015-05-05en
dc.description.abstractCancer cells display aneuploid karyotypes and typically mis-segregate chromosomes at high rates, a phenotype referred to as chromosomal instability (CIN). To test the effects of aneuploidy on chromosome segregation and other mitotic phenotypes we used the colorectal cancer cell line DLD1 (2n = 46) and two variants with trisomy 7 or 13 (DLD1+7 and DLD1+13), as well as euploid and trisomy 13 amniocytes (AF and AF+13). We found that trisomic cells displayed higher rates of chromosome mis-segregation compared to their euploid counterparts. Furthermore, cells with trisomy 13 displayed a distinctive cytokinesis failure phenotype. We showed that up-regulation of SPG20 expression, brought about by trisomy 13 in DLD1+13 and AF+13 cells, is sufficient for the cytokinesis failure phenotype. Overall, our study shows that aneuploidy can induce chromosome mis-segregation. Moreover, we identified a trisomy 13-specific mitotic phenotype that is driven by up-regulation of a gene encoded on the aneuploid chromosome.en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.7554/eLife.05068.001en
dc.identifier.urihttp://hdl.handle.net/10919/84928en
dc.identifier.volume4en
dc.language.isoen_USen
dc.publishereLifeen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectCell biologyen
dc.subjectChromosomes and gene expressionen
dc.subjectAneuploidyen
dc.subjectCanceren
dc.subjectMis-segregationen
dc.subjectCytokinesisen
dc.titleChromosome mis-segregation and cytokinesis failure in trisomic human cellsen
dc.title.serialeLifeen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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