When the genome plays dice: circumvention of the spindle assembly checkpoint and near-random chromosome segregation in multipolar cancer cell mitoses.

<h4>Background</h4>Normal cell division is coordinated by a bipolar mitotic spindle, ensuring symmetrical segregation of chromosomes. Cancer cells, however, occasionally divide into three or more directions. Such multipolar mitoses have been proposed to generate genetic diversity and the...

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Autores principales:	David Gisselsson, Ulf Håkanson, Patrick Stoller, Dominik Marti, Yuesheng Jin, Anders H Rosengren, Ylva Stewénius, Fredrik Kahl, Ioannis Panagopoulos
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6d3f95c8a6834a7a8dbc1d56f9a0d2eb
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spelling	oai:doaj.org-article:6d3f95c8a6834a7a8dbc1d56f9a0d2eb2021-11-25T06:12:53ZWhen the genome plays dice: circumvention of the spindle assembly checkpoint and near-random chromosome segregation in multipolar cancer cell mitoses.1932-620310.1371/journal.pone.0001871https://doaj.org/article/6d3f95c8a6834a7a8dbc1d56f9a0d2eb2008-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18392149/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Normal cell division is coordinated by a bipolar mitotic spindle, ensuring symmetrical segregation of chromosomes. Cancer cells, however, occasionally divide into three or more directions. Such multipolar mitoses have been proposed to generate genetic diversity and thereby contribute to clonal evolution. However, this notion has been little validated experimentally.<h4>Principal findings</h4>Chromosome segregation and DNA content in daughter cells from multipolar mitoses were assessed by multiphoton cross sectioning and fluorescence in situ hybridization in cancer cells and non-neoplastic transformed cells. The DNA distribution resulting from multipolar cell division was found to be highly variable, with frequent nullisomies in the daughter cells. Time-lapse imaging of H2B/GFP-labelled multipolar mitoses revealed that the time from the initiation of metaphase to the beginning of anaphase was prolonged and that the metaphase plates often switched polarity several times before metaphase-anaphase transition. The multipolar metaphase-anaphase transition was accompanied by a normal reduction of cellular cyclin B levels, but typically occurred before completion of the normal separase activity cycle. Centromeric AURKB and MAD2 foci were observed frequently to remain on the centromeres of multipolar ana-telophase chromosomes, indicating that multipolar mitoses were able to circumvent the spindle assembly checkpoint with some sister chromatids remaining unseparated after anaphase. Accordingly, scoring the distribution of individual chromosomes in multipolar daughter nuclei revealed a high frequency of nondisjunction events, resulting in a near-binomial allotment of sister chromatids to the daughter cells.<h4>Conclusion</h4>The capability of multipolar mitoses to circumvent the spindle assembly checkpoint system typically results in a near-random distribution of chromosomes to daughter cells. Spindle multipolarity could thus be a highly efficient generator of genetically diverse minority clones in transformed cell populations.David GisselssonUlf HåkansonPatrick StollerDominik MartiYuesheng JinAnders H RosengrenYlva StewéniusFredrik KahlIoannis PanagopoulosPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 4, p e1871 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q David Gisselsson Ulf Håkanson Patrick Stoller Dominik Marti Yuesheng Jin Anders H Rosengren Ylva Stewénius Fredrik Kahl Ioannis Panagopoulos When the genome plays dice: circumvention of the spindle assembly checkpoint and near-random chromosome segregation in multipolar cancer cell mitoses.
description	<h4>Background</h4>Normal cell division is coordinated by a bipolar mitotic spindle, ensuring symmetrical segregation of chromosomes. Cancer cells, however, occasionally divide into three or more directions. Such multipolar mitoses have been proposed to generate genetic diversity and thereby contribute to clonal evolution. However, this notion has been little validated experimentally.<h4>Principal findings</h4>Chromosome segregation and DNA content in daughter cells from multipolar mitoses were assessed by multiphoton cross sectioning and fluorescence in situ hybridization in cancer cells and non-neoplastic transformed cells. The DNA distribution resulting from multipolar cell division was found to be highly variable, with frequent nullisomies in the daughter cells. Time-lapse imaging of H2B/GFP-labelled multipolar mitoses revealed that the time from the initiation of metaphase to the beginning of anaphase was prolonged and that the metaphase plates often switched polarity several times before metaphase-anaphase transition. The multipolar metaphase-anaphase transition was accompanied by a normal reduction of cellular cyclin B levels, but typically occurred before completion of the normal separase activity cycle. Centromeric AURKB and MAD2 foci were observed frequently to remain on the centromeres of multipolar ana-telophase chromosomes, indicating that multipolar mitoses were able to circumvent the spindle assembly checkpoint with some sister chromatids remaining unseparated after anaphase. Accordingly, scoring the distribution of individual chromosomes in multipolar daughter nuclei revealed a high frequency of nondisjunction events, resulting in a near-binomial allotment of sister chromatids to the daughter cells.<h4>Conclusion</h4>The capability of multipolar mitoses to circumvent the spindle assembly checkpoint system typically results in a near-random distribution of chromosomes to daughter cells. Spindle multipolarity could thus be a highly efficient generator of genetically diverse minority clones in transformed cell populations.
format	article
author	David Gisselsson Ulf Håkanson Patrick Stoller Dominik Marti Yuesheng Jin Anders H Rosengren Ylva Stewénius Fredrik Kahl Ioannis Panagopoulos
author_facet	David Gisselsson Ulf Håkanson Patrick Stoller Dominik Marti Yuesheng Jin Anders H Rosengren Ylva Stewénius Fredrik Kahl Ioannis Panagopoulos
author_sort	David Gisselsson
title	When the genome plays dice: circumvention of the spindle assembly checkpoint and near-random chromosome segregation in multipolar cancer cell mitoses.
title_short	When the genome plays dice: circumvention of the spindle assembly checkpoint and near-random chromosome segregation in multipolar cancer cell mitoses.
title_full	When the genome plays dice: circumvention of the spindle assembly checkpoint and near-random chromosome segregation in multipolar cancer cell mitoses.
title_fullStr	When the genome plays dice: circumvention of the spindle assembly checkpoint and near-random chromosome segregation in multipolar cancer cell mitoses.
title_full_unstemmed	When the genome plays dice: circumvention of the spindle assembly checkpoint and near-random chromosome segregation in multipolar cancer cell mitoses.
title_sort	when the genome plays dice: circumvention of the spindle assembly checkpoint and near-random chromosome segregation in multipolar cancer cell mitoses.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/6d3f95c8a6834a7a8dbc1d56f9a0d2eb
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When the genome plays dice: circumvention of the spindle assembly checkpoint and near-random chromosome segregation in multipolar cancer cell mitoses.

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