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Grant support

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.

Analysis of institutional authors

Zamora-Dorta, MarcosAuthor

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Article

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

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

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

Keywords

Anaphase bridgesBudding yeastCdc14Dna-replicationFork reversalFragile sitesGenomeHolliday junction resolvaseMitotic recombinationProtein localization

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Scientific Reports due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2021, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Multidisciplinary. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-06-05:

  • WoS: 2
  • Scopus: 2
  • OpenCitations: 3

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-05:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 16.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 11 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 8.6.
  • The number of mentions on the social network X (formerly Twitter): 11 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Canada; Denmark.