Institute of Molecular Biology of Barcelona, CSIC, Barcelona, Spain.
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
Commun Biol. 2020 Aug 19;3(1):454. doi: 10.1038/s42003-020-01182-y.
Barrier-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.
着丝粒结合因子（BAF）是一种保守的核膜（NE）成分，它结合染色质并帮助其锚定到 NE。磷酸化和去磷酸化循环控制 BAF 的功能。进入有丝分裂时，磷酸化将 BAF 从染色质上释放出来，并促进 NE 解体。在有丝分裂退出时，PP2A 介导的去磷酸化恢复染色质结合并引发 NE 重新组装。在这里，我们表明在果蝇中，一小部分 BAF（cenBAF）与着丝粒结合。我们还发现，被 CENP-C 招募到着丝粒的 PP4 磷酸酶可防止 cenBAF 在有丝分裂期间发生磷酸化和释放。cenBAF 对于正确的着丝粒组装和准确的染色体分离是必需的，对于有丝分裂进程至关重要。破坏 cenBAF 的定位会阻止 PP2A 在有丝分裂中失活，从而损害全局 BAF 磷酸化，这反过来又导致其与染色质持续结合，延迟后期起始并导致 NE 缺陷。这些结果表明，cenBAF 与 PP4 和 CENP-C 一起形成了一种基于着丝粒的机制，该机制控制着染色体分离和有丝分裂进程。
