
Molecular and Cellular Biology, Год журнала: 2025, Номер unknown, С. 1 - 13
Опубликована: Апрель 24, 2025
Chromosomal instability (CIN), a major hallmark of cancer, can be driven by defects in the integrity centromere or kinetochore structure. Coordinated control phosphorylation and dephosphorylation activities during cell division is critical to ensure chromosomal stability. Overexpression centromeric histone H3 variant CENP-A observed many cancers, its mislocalization noncentromeric regions promotes CIN. We identified protein phosphatase 1 (PP1) nuclear targeting subunit (PNUTS) as top candidate genome-wide siRNA screen for gene depletions that lead increased levels. Here, we define role PNUTS preventing Depletion resulted high levels throughout cycle PP1-dependent manner. Consistent with these results, interacting partner CENP-C were on mitotic chromosomes from PNUTS-depleted cells. Defects CIN phenotypes also Mechanistically, show depletion H3.3 chaperone DAXX suppresses micronuclei incidence In summary, our studies highlight importance phospho-regulation mediated
Язык: Английский