PXD052850-1

PXD052850 is an original dataset announced via ProteomeXchange.

Title	Centromere protection requires strict mitotic inactivation of the Bloom syndrome helicase complex
Description	The BTRR (BLM/TOP3A/RMI1/RMI2) complex resolves various DNA replication and recombination intermediates to suppress genome instability. Alongside PICH, they target mitotic DNA intertwinements, known as ultrafine DNA bridges, facilitating chromosome segregation. Both BLM and PICH undergo transient mitotic hyper-phosphorylation, but the biological significance of this remains elusive. Here, we uncover that during early mitosis, multiple protein kinases act together to strictly constrain the BTRR complex for the protection of centromeres. Mechanistically, CDK1 destabilises the complex and suppresses its association with PICH at the chromatin underneath kinetochores. Inactivating the BLM and TOP3A interaction compromises the UFB-binding complex mitotic functions and can prevent centromere destruction. We further unravel how different clusters of mitotic phosphorylation on BLM affect its interaction with the TOP3A/RMI1/RMI2 subcomplex and illegitimate centromere unwinding. Furthermore, we identify specific phosphorylation sites targeted by the MPS1-PLK1 axis functioning to prevent BLM hyper-activation at centromeres. Notably, unleashing such activity after sister-chromatid cohesion loss facilitates separation of entangled chromosomes. Together, our study defines a centromere protection pathway in human mitotic cells, heavily reliant on a tight spatiotemporal control of the BTRR complex.
HostingRepository	PRIDE
AnnounceDate	2025-08-27
AnnouncementXML	Submission_2025-08-27_03:58:18.178.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Graeme Benstead-Hume
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-05 02:15:58	ID requested
⏵ 1	2025-08-27 03:58:18	announced

10.1038/S41467-025-62966-6;

submitter keyword: chromosome biorientation, Bloom syndrome helicase, CDK1, MPS1, PICH,PLK1, ultrafine DNA bridge (UFB)-binding complex, PP1s, RIF1, anaphase DNA bridges, centromeres, BTRR dissolvasome

Jyoti Choudhary
contact affiliation	Functional Proteomics, ICR
contact email	jyoti.choudhary@icr.ac.uk
lab head
Graeme Benstead-Hume
contact affiliation	ICR
contact email	ghume@icr.ac.uk
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/2025/08/PXD052850

PRIDE project URI

• PRIDE
  1. PXD052850
     1. Label: PRIDE project
     2. Name: Centromere protection requires strict mitotic inactivation of the Bloom syndrome helicase complex