Marseille Cancer Research Center (CRCM), U1068 Inserm, UMR7258 CNRS, Aix-Marseille Université, Institut Paoli-Calmettes, Equipe Labellisée Ligue, Marseille, France
Instituto de Biomedicina de Sevilla, Hospital Virgen del Rocío-CSIC-Universidad de Sevilla, Sevilla, Spain
Trinidad Sanmartín Olmo
Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain
Frederic Jourquin
Marseille Cancer Research Center (CRCM), U1068 Inserm, UMR7258 CNRS, Aix-Marseille Université, Institut Paoli-Calmettes, Equipe Labellisée Ligue, Marseille, France
Maria Cruz Muñoz Centeno
Instituto de Biomedicina de Sevilla, Hospital Virgen del Rocío-CSIC-Universidad de Sevilla, Sevilla, Spain
Manuel Mendoza
Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain
Marie-Noelle Simon
Marseille Cancer Research Center (CRCM), U1068 Inserm, UMR7258 CNRS, Aix-Marseille Université, Institut Paoli-Calmettes, Equipe Labellisée Ligue, Marseille, France
Sebastian Chavez
Instituto de Biomedicina de Sevilla, Hospital Virgen del Rocío-CSIC-Universidad de Sevilla, Sevilla, Spain
Marseille Cancer Research Center (CRCM), U1068 Inserm, UMR7258 CNRS, Aix-Marseille Université, Institut Paoli-Calmettes, Equipe Labellisée Ligue, Marseille, France
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.
