Accurate chromosome segregation requires the attachment of microtubules to centromeres, epigenetically defined by the enrichment of CENP-A nucleosomes. During DNA replication, CENP-A nucleosomes undergo dilution. To preserve centromere identity, correct amounts of CENP-A must be restored in a cell cycle–controlled manner orchestrated by the Mis18 complex (Mis18α-Mis18β-Mis18BP1). We demonstrate here that PLK1 interacts with the Mis18 complex by recognizing self-primed phosphorylations of Mis18α (Ser 54 ) and Mis18BP1 (Thr 78 and Ser 93 ) through its Polo-box domain. Disrupting these phosphorylations perturbed both centromere recruitment of the CENP-A chaperone HJURP and new CENP-A loading. Biochemical and functional analyses showed that phosphorylation of Mis18α and PLK1 binding were required to activate Mis18α-Mis18β and promote Mis18 complex-HJURP interaction. Thus, our study reveals key molecular events underpinning the licensing role of PLK1 in ensuring accurate centromere inheritance.

中文翻译：

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PLK1介导的磷酸化级联激活Mis18复合物以确保着丝粒遗传


准确的染色体分离需要将微管附着到着丝粒上，这在表观遗传学上是由 CENP-A 核小体的富集来定义的。 DNA 复制过程中，CENP-A 核小体会被稀释。为了保持着丝粒的身份，必须以由 Mis18 复合体（Mis18α-Mis18β-Mis18BP1）协调的细胞周期控制方式恢复正确数量的 CENP-A。我们在此证明，PLK1 通过其 Polo-box 结构域识别 Mis18α (Ser 54 ) 和 Mis18BP1 (Thr 78 和 Ser 93 ) 的自引发磷酸化，从而与 Mis18 复合物相互作用。破坏这些磷酸化会扰乱 CENP-A 伴侣 HJURP 的着丝粒募集和新的 CENP-A 加载。生化和功能分析表明，Mis18α 和 PLK1 结合的磷酸化是激活 Mis18α-Mis18β 并促进 Mis18 复合物-HJURP 相互作用所必需的。因此，我们的研究揭示了支持 PLK1 在确保着丝粒准确遗传方面的许可作用的关键分子事件。