High levels of histones promote whole-genome-duplications and trigger a Swe1<sup>WEE1</sup>-dependent phosphorylation of Cdc28<sup>CDK1</sup>.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29580382.
- Also identified by DOI 10.7554/eLife.35337 and PMC identifier 5871333.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>Saccharomyces cerevisiae</i> 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 Swe1<sup>WEE1</sup> stabilisation thereby triggering the phosphorylation and inhibition of Cdc28<sup>CDK1</sup> 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.
Medical subject headings
- CDC28 Protein Kinase, S cerevisiae
- Cell Cycle Proteins
- Chromosome Duplication
- Histones
- Protein Processing, Post-Translational
- Protein-Tyrosine Kinases
- Saccharomyces cerevisiae
- Saccharomyces cerevisiae Proteins