High levels of histones promote whole-genome-duplications and trigger a Swe1(WEE1)-dependent phosphorylation of Cdc213(CDK1)
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- dc.contributor.author Maya Miles, Douglas
- dc.contributor.author Peñate, Xenia
- dc.contributor.author Sanmartín Olmo, Trinidad
- dc.contributor.author Jourquin, Frederic
- dc.contributor.author Muñoz Centeno, Maria Cruz
- dc.contributor.author Mendoza, Manuel (Mendoza Palomares)
- dc.contributor.author Simon, Marie-Noelle
- dc.contributor.author Chávez, Sebastián
- dc.contributor.author Geli, Vincent
- dc.date.accessioned 2019-11-14T13:24:32Z
- dc.date.available 2019-11-14T13:24:32Z
- dc.date.issued 2018
- dc.description.abstract Whole-genome duplications (WGDs) have played a central role in the evolution of genomes and constitute an important source of genome instability in cancer. Here, we show in Saccharomyces cerevisiae that abnormal accumulations of histones are sufficient to induce WGDs. Our results link these WGDs to a reduced incorporation of the histone variant H2A.Z to chromatin. Moreover, we show that high levels of histones promote Swe1WEE1 stabilisation thereby triggering the phosphorylation and inhibition of Cdc28CDK1 through a mechanism different of the canonical DNA damage response. Our results link high levels of histones to a specific type of genome instability that is quite frequently observed in cancer and uncovers a new mechanism that might be able to respond to high levels of histones.
- dc.description.sponsorship We thank A Gunjan, J Tyler, S Biggins, F Prado, Doug Kellogg, and S Mahajan for sharing strains, plasmids and/or reagents; We would also like to thank C Machu for imaging expertise and JH Guervilly, Felix Prado, E Bailly and V Geli team members for discussions. DM was supported by a postdoctoral fellowship from the Association pour la Recherche sur le Cancer (Fondation ARC). Work in VG laboratory is supported by the”Ligue contre le Cancer’ (Equipe Labéllisée 2017). Work in the laboratory of M M is supported of the European Research Council (ERC) Starting Grant 2010-St-20091118, and the Spanish Ministry of Economy and Competitiveness BFU2012-37162 to MM, and ‘Centro de Excelencia Severo Ochoa 2013–2017’, SEV-2012–0208 to the CRG. S C is supported by grants BFU2013-48643-C3-1-P from the Spanish MiNECO, and P12-BIO1938MO from the Regional Andalusian Government, both incluidng European Union funds (FEDER).
- dc.format.mimetype application/pdf
- dc.identifier.citation Maya Miles D, Peñate X, Sanmartín Olmo T, Jourquin F, Muñoz Centeno MC, Mendoza M et al. High levels of histones promote whole-genome-duplications and trigger a Swe1(WEE1)-dependent phosphorylation of Cdc213(CDK1). eLife 2018;7:e35337. DOI: 10.7554/eLife.35337.001
- dc.identifier.doi http://dx.doi.org/10.7554/eLife.35337.001
- dc.identifier.issn 2050-084X
- dc.identifier.uri http://hdl.handle.net/10230/42848
- dc.language.iso eng
- dc.publisher eLife
- dc.relation.ispartof eLife 2018;7:e35337
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2012-37162
- dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2013-48643-C3-1-P
- dc.rights © 2018, Maya Miles et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Chromosomes
- dc.subject.keyword Genes
- dc.subject.keyword Histones
- dc.title High levels of histones promote whole-genome-duplications and trigger a Swe1(WEE1)-dependent phosphorylation of Cdc213(CDK1)
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion