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Chromosome mis-segregation and cytokinesis failure in trisomic human cells

Cancer 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) a...

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Autores principales: Nicholson, Joshua M, Macedo, Joana C, Mattingly, Aaron J, Wangsa, Darawalee, Camps, Jordi, Lima, Vera, Gomes, Ana M, Dória, Sofia, Ried, Thomas, Logarinho, Elsa, Cimini, Daniela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443816/
https://www.ncbi.nlm.nih.gov/pubmed/25942454
http://dx.doi.org/10.7554/eLife.05068
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author Nicholson, Joshua M
Macedo, Joana C
Mattingly, Aaron J
Wangsa, Darawalee
Camps, Jordi
Lima, Vera
Gomes, Ana M
Dória, Sofia
Ried, Thomas
Logarinho, Elsa
Cimini, Daniela
author_facet Nicholson, Joshua M
Macedo, Joana C
Mattingly, Aaron J
Wangsa, Darawalee
Camps, Jordi
Lima, Vera
Gomes, Ana M
Dória, Sofia
Ried, Thomas
Logarinho, Elsa
Cimini, Daniela
author_sort Nicholson, Joshua M
collection PubMed
description Cancer 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. DOI: http://dx.doi.org/10.7554/eLife.05068.001
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spelling pubmed-44438162015-05-27 Chromosome mis-segregation and cytokinesis failure in trisomic human cells Nicholson, Joshua M Macedo, Joana C Mattingly, Aaron J Wangsa, Darawalee Camps, Jordi Lima, Vera Gomes, Ana M Dória, Sofia Ried, Thomas Logarinho, Elsa Cimini, Daniela eLife Cell Biology Cancer 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. DOI: http://dx.doi.org/10.7554/eLife.05068.001 eLife Sciences Publications, Ltd 2015-05-05 /pmc/articles/PMC4443816/ /pubmed/25942454 http://dx.doi.org/10.7554/eLife.05068 Text en http://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (http://creativecommons.org/publicdomain/zero/1.0/) .
spellingShingle Cell Biology
Nicholson, Joshua M
Macedo, Joana C
Mattingly, Aaron J
Wangsa, Darawalee
Camps, Jordi
Lima, Vera
Gomes, Ana M
Dória, Sofia
Ried, Thomas
Logarinho, Elsa
Cimini, Daniela
Chromosome mis-segregation and cytokinesis failure in trisomic human cells
title Chromosome mis-segregation and cytokinesis failure in trisomic human cells
title_full Chromosome mis-segregation and cytokinesis failure in trisomic human cells
title_fullStr Chromosome mis-segregation and cytokinesis failure in trisomic human cells
title_full_unstemmed Chromosome mis-segregation and cytokinesis failure in trisomic human cells
title_short Chromosome mis-segregation and cytokinesis failure in trisomic human cells
title_sort chromosome mis-segregation and cytokinesis failure in trisomic human cells
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443816/
https://www.ncbi.nlm.nih.gov/pubmed/25942454
http://dx.doi.org/10.7554/eLife.05068
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