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The histone H3.3 K27M mutation suppresses Ser31phosphorylation and mitotic fidelity, which can directly drive gliomagenesis.

ABSTRACT: Serine 31 is a phospho-site unique to the histone H3.3 variant; mitotic phospho-Ser31 is restricted to pericentromeric heterochromatin, and disruption of phospho-Ser31 results in chromosome segregation defects and loss of p53-dependant G₁ cell-cycle arrest.¹^,²^,³^,⁴ Ser31 is proximal to the H3.3 lysine 27-to-methionine (K27M) mutation that drives ∼80% of pediatric diffuse midline gliomas.⁵^,⁶^,⁷^,⁸^,⁹^,¹⁰^,¹¹^,¹² Here, we show that expression of the H3.3 K27M mutant in normal, diploid cells results in increased chromosome missegregation and failure t

SUBMITTER: Day CA

PROVIDER: S-EPMC12673919 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature

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The histone H3.3 K27M mutation suppresses Ser31phosphorylation and mitotic fidelity, which can directly drive gliomagenesis.

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