PXD053141-2

PXD053141 is an original dataset announced via ProteomeXchange.

Title	PLK1-Mediated Phosphorylation Cascade Activates the Mis18 Complex to Ensure Centromere Inheritance
Description	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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:57:49.634.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Juan Zou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-15 15:46:35	ID requested
1	2024-09-09 05:10:00	announced
⏵ 2	2024-10-22 06:57:50	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: mass spectrometry,PLK1 phosphorylation, human Mis18α/β complex

Juri Rappsilber
contact affiliation	Room 4.17 Michael Swann Building The University of Edinburgh Max Born Crescent Edinburgh EH9 3BF
contact email	juri.rappsilber@ed.ac.uk
lab head
Juan Zou
contact affiliation	The University of Edinburgh
contact email	jzou@ed.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053141
     1. Label: PRIDE project
     2. Name: PLK1-Mediated Phosphorylation Cascade Activates the Mis18 Complex to Ensure Centromere Inheritance