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We thank other members of the lab for fruitful discussions and help. This work was supported by the Spanish Ministry of Science and Innovation research grants BFU2015-63902-R and BFU2017-83954-R to F. M., the Danish Council for Independent Research, the Carlsberg Foundation and the Villum Foundation to M.L. and O.Q., and Canadian Institutes of Health Research grant FDN-159913 to G.W. B. High-throughput imaging was performed at the Center for Advanced Bioimaging, University of Copenhagen. Agencia Canaria de Investigacion, Innovacion y Sociedad de la Informacion supported C.R-P., S.S-S. and S.M-S. through predoctoral fellowships (TESIS20120109, TESIS2018010034 and TESIS2020010028, respectively). Grants to F.M. and predoctoral fellowships were co-financed with the European Commission's ERDF structural funds.

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

Publicado en:Scientific Reports. 11 (1): 14940- - 2021-12-01 11(1), DOI: 10.1038/s41598-021-93875-5

Autores: Ayra-Plasencia, Jessel; Ramos-Perez, Cristina; Santana-Sosa, Silvia; Quevedo, Oliver; Medina-Suarez, Sara; Matos-Perdomo, Emiliano; Zamora-Dorta, Marcos; Brown, Grant W; Lisby, Michael; Machin, Felix

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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 G(2)/M checkpoint. We propose that the absence of Top2 activity leads to a general chromosome structural/topological change in mitosis.

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