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PLK1-Mediated Phosphorylation Cascade Activates the Mis18 Complex to Ensure Centromere Inheritance

ABSTRACT: Accurate chromosome segregation requires the attachment of spindle microtubules to 20 centromeres, which are epigenetically defined by the enrichment of CENP-A nucleosomes. During DNA replication, existing CENP-A nucleosomes undergo dilution as they get redistributed among the two DNA strands. To preserve centromere identity, CENP-A levels must be restored in a cellcycle controlled manner orchestrated by the Mis18 complex. Here we provide a comprehensive mechanistic basis for PLK1-mediated licensing of CENP-A loading. We demonstrate that PLK1 25 interacts with Mis18α and Mis18BP1 subunits of the Mis18 complex by recognising self-primed phosphorylations of Mis18α (S54) and Mis18BP1 (T78 and S93) through its Polo-box binding domain. Disrupting these PLK1 phosphorylations perturbed the centromere recruitment of HJURP and new CENP-A loading. Biochemical and functional analyses show that phosphorylation of Mis18α and subsequent PLK1 binding is required to activate the Mis18α/β complex for robust 30 Mis18α/β-HJURP interaction. Thus, our study reveals key molecular events underpinning the licensing role of PLK1 in ensuring accurate centromere inheritance.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Juan Zou

LAB HEAD: Juri Rappsilber

PROVIDER: PXD053141 | Pride | 2024-09-09

REPOSITORIES: Pride

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			Action	DRS
	Mis18AB_FL_Mis18BP1_490_Plk1.fasta	Fasta
	Mis18AB_FL_Plk1.fasta	Fasta
	Mis18BP1_490_Plk1.fasta	Fasta
	Zou_Rappsilber_JP_Mis18AB_MisBP1_490_Phos_Plk1.xlsx	Xlsx
	Zou_Rappsilber_JP_Mis18AB_MisBP1_490_Phos_Plk1_R1.raw	Raw

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