Oncohistone H3 E97K mutation facilitates CENP-A mislocalization and chromosomal instability in budding yeast.

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

SUBMITTER: Ohkuni K 

PROVIDER: S-EPMC11822376 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature