High levels of histones promote whole-genome-duplications and trigger a Swe1(WEE1)-dependent phosphorylation of Cdc213(CDK1)

Maya Miles, Douglas; Peñate, Xenia; Sanmartín Olmo, Trinidad; Jourquin, Frederic; Muñoz Centeno, Maria Cruz; Mendoza, Manuel (Mendoza Palomares); Simon, Marie-Noelle; Chávez, Sebastián; Geli, Vincent

doi:http://dx.doi.org/10.7554/eLife.35337.001

High levels of histones promote whole-genome-duplications and trigger a Swe1(WEE1)-dependent phosphorylation of Cdc213(CDK1)

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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

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.