PXD053197

PXD053197 is an original dataset announced via ProteomeXchange.

Title	PLK1-Mediated Phosphorylation Cascade Activates Mis18 Complex to Ensure Centromere Inheritance
Description	Accurate chromosome segregation requires the attachment of spindle microtubules to 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 cell-cycle 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 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 Mis18α/β-HJURP interaction. Thus, our study reveals key molecular events underpinning the licensing role of PLK1 in ensuring accurate centromere inheritance.
HostingRepository	PRIDE
AnnounceDate	2025-02-15
AnnouncementXML	Submission_2025-02-15_14:42:31.776.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christos Spanos
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-18 03:55:43	ID requested
⏵ 1	2025-02-15 14:42:32	announced

10.1126/SCIENCE.ADO8270;

submitter keyword: HJURP,PLK1, Mis18, phosphorylation, cross-linking mass spectrometer

Jeyaprakash Arulanandam
contact affiliation	University of Edinburgh
contact email	jeyaprakash.arulanandam@ed.ac.uk
lab head
Christos Spanos
contact affiliation	University of Edinburgh
contact email	spanos.christos@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/02/PXD053197

PRIDE project URI

• PRIDE
  1. PXD053197
     1. Label: PRIDE project
     2. Name: PLK1-Mediated Phosphorylation Cascade Activates Mis18 Complex to Ensure Centromere Inheritance