Topoisomerase II deficiency leads to a postreplicative structural shift in all Saccharomyces cerevisiae chromosomes

Abstract The key role of Topoisomerase II (Top2) is the removal of topological intertwines between sister chromatids. In yeast, inactivation of Top2 brings about distinct cell cycle responses. In the case of the conditional top2-5 allele, interphase and mitosis progress on schedule but cells suffer...

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Autores principales:	Jessel Ayra-Plasencia, Cristina Ramos-Pérez, Silvia Santana-Sosa, Oliver Quevedo, Sara Medina-Suárez, Emiliano Matos-Perdomo, Marcos Zamora-Dorta, Grant W. Brown, Michael Lisby, Félix Machín
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7c08ad1d2a4f43afa57021c0e2001c32
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spelling	oai:doaj.org-article:7c08ad1d2a4f43afa57021c0e2001c322021-12-02T17:55:03ZTopoisomerase II deficiency leads to a postreplicative structural shift in all Saccharomyces cerevisiae chromosomes10.1038/s41598-021-93875-52045-2322https://doaj.org/article/7c08ad1d2a4f43afa57021c0e2001c322021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93875-5https://doaj.org/toc/2045-2322Abstract The key role of Topoisomerase II (Top2) is the removal of topological intertwines between sister chromatids. In yeast, inactivation of Top2 brings about distinct cell cycle responses. In the case of the conditional top2-5 allele, interphase and mitosis progress on schedule but cells suffer from a chromosome segregation catastrophe. We here show that top2-5 chromosomes fail to enter a Pulsed-Field Gel Electrophoresis (PFGE) in the first cell cycle, a behavior traditionally linked to the presence of replication and recombination intermediates. We distinguished two classes of affected chromosomes: the rDNA-bearing chromosome XII, which fails to enter a PFGE at the beginning of S-phase, and all the other chromosomes, which fail at a postreplicative stage. In synchronously cycling cells, this late PFGE retention is observed in anaphase; however, we demonstrate that this behavior is independent of cytokinesis, stabilization of anaphase bridges, spindle pulling forces and, probably, anaphase onset. Strikingly, once the PFGE retention has occurred it becomes refractory to Top2 re-activation. DNA combing, two-dimensional electrophoresis, genetic analyses, and GFP-tagged DNA damage markers suggest that neither recombination intermediates nor unfinished replication account for the postreplicative PFGE shift, which is further supported by the fact that the shift does not trigger the G2/M checkpoint. We propose that the absence of Top2 activity leads to a general chromosome structural/topological change in mitosis.Jessel Ayra-PlasenciaCristina Ramos-PérezSilvia Santana-SosaOliver QuevedoSara Medina-SuárezEmiliano Matos-PerdomoMarcos Zamora-DortaGrant W. BrownMichael LisbyFélix MachínNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jessel Ayra-Plasencia Cristina Ramos-Pérez Silvia Santana-Sosa Oliver Quevedo Sara Medina-Suárez Emiliano Matos-Perdomo Marcos Zamora-Dorta Grant W. Brown Michael Lisby Félix Machín Topoisomerase II deficiency leads to a postreplicative structural shift in all Saccharomyces cerevisiae chromosomes
description	Abstract The key role of Topoisomerase II (Top2) is the removal of topological intertwines between sister chromatids. In yeast, inactivation of Top2 brings about distinct cell cycle responses. In the case of the conditional top2-5 allele, interphase and mitosis progress on schedule but cells suffer from a chromosome segregation catastrophe. We here show that top2-5 chromosomes fail to enter a Pulsed-Field Gel Electrophoresis (PFGE) in the first cell cycle, a behavior traditionally linked to the presence of replication and recombination intermediates. We distinguished two classes of affected chromosomes: the rDNA-bearing chromosome XII, which fails to enter a PFGE at the beginning of S-phase, and all the other chromosomes, which fail at a postreplicative stage. In synchronously cycling cells, this late PFGE retention is observed in anaphase; however, we demonstrate that this behavior is independent of cytokinesis, stabilization of anaphase bridges, spindle pulling forces and, probably, anaphase onset. Strikingly, once the PFGE retention has occurred it becomes refractory to Top2 re-activation. DNA combing, two-dimensional electrophoresis, genetic analyses, and GFP-tagged DNA damage markers suggest that neither recombination intermediates nor unfinished replication account for the postreplicative PFGE shift, which is further supported by the fact that the shift does not trigger the G2/M checkpoint. We propose that the absence of Top2 activity leads to a general chromosome structural/topological change in mitosis.
format	article
author	Jessel Ayra-Plasencia Cristina Ramos-Pérez Silvia Santana-Sosa Oliver Quevedo Sara Medina-Suárez Emiliano Matos-Perdomo Marcos Zamora-Dorta Grant W. Brown Michael Lisby Félix Machín
author_facet	Jessel Ayra-Plasencia Cristina Ramos-Pérez Silvia Santana-Sosa Oliver Quevedo Sara Medina-Suárez Emiliano Matos-Perdomo Marcos Zamora-Dorta Grant W. Brown Michael Lisby Félix Machín
author_sort	Jessel Ayra-Plasencia
title	Topoisomerase II deficiency leads to a postreplicative structural shift in all Saccharomyces cerevisiae chromosomes
title_short	Topoisomerase II deficiency leads to a postreplicative structural shift in all Saccharomyces cerevisiae chromosomes
title_full	Topoisomerase II deficiency leads to a postreplicative structural shift in all Saccharomyces cerevisiae chromosomes
title_fullStr	Topoisomerase II deficiency leads to a postreplicative structural shift in all Saccharomyces cerevisiae chromosomes
title_full_unstemmed	Topoisomerase II deficiency leads to a postreplicative structural shift in all Saccharomyces cerevisiae chromosomes
title_sort	topoisomerase ii deficiency leads to a postreplicative structural shift in all saccharomyces cerevisiae chromosomes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7c08ad1d2a4f43afa57021c0e2001c32
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Topoisomerase II deficiency leads to a postreplicative structural shift in all Saccharomyces cerevisiae chromosomes

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