Dual Role of Topoisomerase II in Centromere Resolution and Aurora B Activity

Detalhes bibliográficos
Autor(a) principal: Coelho, PA
Data de Publicação: 2008
Outros Autores: Queiroz-Machado, J, Carmo, AM, Moutinho-Pereira, S, Maiato, H, Sunkel, CE
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10216/27683
Resumo: 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.
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spelling Dual Role of Topoisomerase II in Centromere Resolution and Aurora B ActivityChromosome 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.20082008-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10216/27683eng1544-9173Coelho, PAQueiroz-Machado, JCarmo, AMMoutinho-Pereira, SMaiato, HSunkel, CEinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-29T15:53:48Zoai:repositorio-aberto.up.pt:10216/27683Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:34:49.144868Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Dual Role of Topoisomerase II in Centromere Resolution and Aurora B Activity
title Dual Role of Topoisomerase II in Centromere Resolution and Aurora B Activity
spellingShingle Dual Role of Topoisomerase II in Centromere Resolution and Aurora B Activity
Coelho, PA
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
author Coelho, PA
author_facet Coelho, PA
Queiroz-Machado, J
Carmo, AM
Moutinho-Pereira, S
Maiato, H
Sunkel, CE
author_role author
author2 Queiroz-Machado, J
Carmo, AM
Moutinho-Pereira, S
Maiato, H
Sunkel, CE
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Coelho, PA
Queiroz-Machado, J
Carmo, AM
Moutinho-Pereira, S
Maiato, H
Sunkel, CE
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.
publishDate 2008
dc.date.none.fl_str_mv 2008
2008-01-01T00:00:00Z
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