A fraction of barrier-to-autointegration factor (BAF) associates with centromeres and controls mitosis progression

• DOI: 10.1038/s42003-020-01182-y
• Publication Date: 2020-08-19T10:03:35Z
• Authors: Mònica Torras-Llort; Sònia Medina-Giró; Paula Escudero-Fe...; Zoltan Lipinszki; Olga Moreno-Moreno; Zoltan Karman; Marcin R. Przewloka; Fernando Azorín
• Keywords: 0301 basic medicine; 570; Cell biology; QH3015 Molecular biology / molekuláris biológia; Centromere; Fluorescent Antibody Technique; Mitosis; Nuclear Proteins; Models, Biological; Article; Chromatin; Chromosome segregation; DNA-Binding Proteins; Protein Transport; 03 medical and health sciences; Gene Expression Regulation; Animals; Drosophila Proteins; Phosphorylation; Biomarkers; Protein Binding

AbstractBarrier-to-Autointegration Factor (BAF) is a conserved nuclear envelope (NE) component that binds chromatin and helps its anchoring to the NE. Cycles of phosphorylation and dephosphorylation control BAF function. Entering mitosis, phosphorylation releases BAF from chromatin and facilitates NE-disassembly. At mitotic exit, PP2A-mediated dephosphorylation restores chromatin binding and nucleates NE-reassembly. Here, we show that in Drosophila a small fraction of BAF (cenBAF) associates with centromeres. We also find that PP4 phosphatase, which is recruited to centromeres by CENP-C, prevents phosphorylation and release of cenBAF during mitosis. cenBAF is necessary for proper centromere assembly and accurate chromosome segregation, being critical for mitosis progression. Disrupting cenBAF localization prevents PP2A inactivation in mitosis compromising global BAF phosphorylation, which in turn leads to its persistent association with chromatin, delays anaphase onset and causes NE defects. These results suggest that, together with PP4 and CENP-C, cenBAF forms a centromere-based mechanism that controls chromosome segregation and mitosis progression.