ArticleNucleic acids research2025
Oncohistone H3 E97K mutation facilitates CENP-A mislocalization and chromosomal instability in budding yeast.
Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Epigenetic regulation of metabolism in Saccharomyces cerevisiae: mechanisms, metabolic crosstalk, and engineering applications.Molecular biology reports · 2026Review
- Keeping it centered: decoding the activities that regulate yeast histone H3 variant Cse4 and confine it to centromeres.Frontiers in cell and developmental biology · 2026Review
- Chromatin remodeling activity of EP400 safeguards chromosomal stability by preventing CENP-A mislocalization.Cell reports · 2025Article
- Characterization of oncohistone H2B variants in Schizosaccharomyces pombe reveals a key role of H2B monoubiquitination deficiency in genomic instability by altering gene expression.FEMS yeast research · 2025Article
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5 authors.
Funding
Abstract
Mislocalization of overexpressed CENP-A (Cse4 in budding yeast) contributes to chromosomal instability (CIN) in yeasts, flies, and human cells. Overexpression of CENP-A is observed in many cancers and this correlates with poor prognosis. Here, we show that altered stoichiometry of histone H3 and expression of oncohistone mutation H3 E97K contributes to mislocalization of Cse4 and CIN. Oncohistone mutations in the globular domain of histone H3 such as H3 E97K occur in several cancers; however, their functional effects remain unexplored. We demonstrated that strains with reduced gene dosage of histone H3 (hht1Δ and hht2Δ) or oncohistone H3 E97K mutation exhibit enhanced Cse4-H4 interaction, an in vivo change in the conformational state of Cse4, and this contributes to mislocalization of Cse4. Oncohistone H3 E97K mutant protein was unstable and exhibited defects in interaction with histone H4. Notably, mislocalization of Cse4 and CIN phenotypes were observed in hht1Δ and oncohistone H3 E97K mutants expressing endogenous Cse4. In summary, our studies highlight the importance of histone H3 stoichiometry in preventing mislocalization of Cse4 for chromosomal stability and suggest that oncohistone H3 mutations may contribute to CIN in human cancers.
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