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) and Mis18BP1 (Thr and Ser) 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.
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PLK1-mediated phosphorylation cascade activates Mis18 complex to ensure centromere inheritance.
Science
September 2024
Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, UK.
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).
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EMBO Rep
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Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, EH9 3BF, UK.
Article Synopsis
- - The centromere, crucial for chromosome stability, relies on CENP-A-containing nucleosomes for proper microtubule attachment during cell division.
- - The Mis18 complex, consisting of Mis18α, Mis18β, and Mis18BP1, plays a key role in maintaining centromere identity by facilitating CENP-A loading through its specific chaperone, HJURP.
- - Research reveals the structure of the Mis18 complex and identifies key interactions needed for assembly and function, emphasizing that while Mis18α can associate with the centromere independently, Mis18β is essential for effective CENP-A loading.
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