A Saccharomyces cerevisiae model and screen to define the functional consequences of oncogenic histone missense mutations.

ABSTRACT: Somatic missense mutations in histone genes turn these essential proteins into oncohistones, which can drive oncogenesis. Understanding how missense mutations alter histone function is challenging in mammals as mutations occur in a single histone gene. For example, described oncohistone mutations predominantly occur in the histone H3.3 gene, despite the human genome encoding 15 H3 genes. To understand how oncogenic histone missense mutations alter histone function, we leveraged the budding yeast model, which contains only 2 H3 genes, to explore the functional consequences of oncohistones H3K36M, H3G34W, H3G34L, H3G34R, and H3G34V. Analysis of cells that express each of these variants as the sole copy of H3 reveals that H3K36 mutants show different drug sensitivities compared to H3G34 mutan

SUBMITTER: Lemon LD 

PROVIDER: S-EPMC9258546 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature