Dual role of topoisomerase II in centromere resolution and aurora B activity.

Chromosome segregation requires sister chromatid resolution. Condensins are essential for this process since they organize an axial structure where topoisomerase II can work. How sister chromatid separation is coordinated with chromosome condensation and decatenation activity remains unknown. We com...

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Autores principales:	Paula A Coelho, Joana Queiroz-Machado, Alexandre M Carmo, Sara Moutinho-Pereira, Helder Maiato, Claudio E Sunkel
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c2425f9c41bf43d99a483c9dd002442a
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spelling	oai:doaj.org-article:c2425f9c41bf43d99a483c9dd002442a2021-11-25T05:33:58ZDual role of topoisomerase II in centromere resolution and aurora B activity.1544-91731545-788510.1371/journal.pbio.0060207https://doaj.org/article/c2425f9c41bf43d99a483c9dd002442a2008-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18752348/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Chromosome segregation requires sister chromatid resolution. Condensins are essential for this process since they organize an axial structure where topoisomerase II can work. How sister chromatid separation is coordinated with chromosome condensation and decatenation activity remains unknown. We combined four-dimensional (4D) microscopy, RNA interference (RNAi), and biochemical analyses to show that topoisomerase II plays an essential role in this process. Either depletion of topoisomerase II or exposure to specific anti-topoisomerase II inhibitors causes centromere nondisjunction, associated with syntelic chromosome attachments. However, cells degrade cohesins and timely exit mitosis after satisfying the spindle assembly checkpoint. Moreover, in topoisomerase II-depleted cells, Aurora B and INCENP fail to transfer to the central spindle in late mitosis and remain tightly associated with centromeres of nondisjoined sister chromatids. Also, in topoisomerase II-depleted cells, Aurora B shows significantly reduced kinase activity both in S2 and HeLa cells. Codepletion of BubR1 in S2 cells restores Aurora B kinase activity, and consequently, most syntelic attachments are released. Taken together, our results support that topoisomerase II ensures proper sister chromatid separation through a direct role in centromere resolution and prevents incorrect microtubule-kinetochore attachments by allowing proper activation of Aurora B kinase.Paula A CoelhoJoana Queiroz-MachadoAlexandre M CarmoSara Moutinho-PereiraHelder MaiatoClaudio E SunkelPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 6, Iss 8, p e207 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Paula A Coelho Joana Queiroz-Machado Alexandre M Carmo Sara Moutinho-Pereira Helder Maiato Claudio E Sunkel Dual role of topoisomerase II in centromere resolution and aurora B activity.
description	Chromosome segregation requires sister chromatid resolution. Condensins are essential for this process since they organize an axial structure where topoisomerase II can work. How sister chromatid separation is coordinated with chromosome condensation and decatenation activity remains unknown. We combined four-dimensional (4D) microscopy, RNA interference (RNAi), and biochemical analyses to show that topoisomerase II plays an essential role in this process. Either depletion of topoisomerase II or exposure to specific anti-topoisomerase II inhibitors causes centromere nondisjunction, associated with syntelic chromosome attachments. However, cells degrade cohesins and timely exit mitosis after satisfying the spindle assembly checkpoint. Moreover, in topoisomerase II-depleted cells, Aurora B and INCENP fail to transfer to the central spindle in late mitosis and remain tightly associated with centromeres of nondisjoined sister chromatids. Also, in topoisomerase II-depleted cells, Aurora B shows significantly reduced kinase activity both in S2 and HeLa cells. Codepletion of BubR1 in S2 cells restores Aurora B kinase activity, and consequently, most syntelic attachments are released. Taken together, our results support that topoisomerase II ensures proper sister chromatid separation through a direct role in centromere resolution and prevents incorrect microtubule-kinetochore attachments by allowing proper activation of Aurora B kinase.
format	article
author	Paula A Coelho Joana Queiroz-Machado Alexandre M Carmo Sara Moutinho-Pereira Helder Maiato Claudio E Sunkel
author_facet	Paula A Coelho Joana Queiroz-Machado Alexandre M Carmo Sara Moutinho-Pereira Helder Maiato Claudio E Sunkel
author_sort	Paula A Coelho
title	Dual role of topoisomerase II in centromere resolution and aurora B activity.
title_short	Dual role of topoisomerase II in centromere resolution and aurora B activity.
title_full	Dual role of topoisomerase II in centromere resolution and aurora B activity.
title_fullStr	Dual role of topoisomerase II in centromere resolution and aurora B activity.
title_full_unstemmed	Dual role of topoisomerase II in centromere resolution and aurora B activity.
title_sort	dual role of topoisomerase ii in centromere resolution and aurora b activity.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/c2425f9c41bf43d99a483c9dd002442a
work_keys_str_mv	AT paulaacoelho dualroleoftopoisomeraseiiincentromereresolutionandaurorabactivity AT joanaqueirozmachado dualroleoftopoisomeraseiiincentromereresolutionandaurorabactivity AT alexandremcarmo dualroleoftopoisomeraseiiincentromereresolutionandaurorabactivity AT saramoutinhopereira dualroleoftopoisomeraseiiincentromereresolutionandaurorabactivity AT heldermaiato dualroleoftopoisomeraseiiincentromereresolutionandaurorabactivity AT claudioesunkel dualroleoftopoisomeraseiiincentromereresolutionandaurorabactivity
_version_	1718414601562882048

Dual role of topoisomerase II in centromere resolution and aurora B activity.

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