PXD064192-1

PXD064192 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 BTRR complex activities at 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 mitotic phosphorylation sites of BLM affect its interaction with the TOP3A/RMI1/RMI2 subcomplex and centromeric DNA unwinding. Furthermore, we show that multiple PLK1-mediated phosphorylation on BLM is required to suppress aberrant centromere unwinding. However, 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	2025-08-12
AnnouncementXML	Submission_2025-08-12_03:38:06.263.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD064192
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Umit Aliyaskarova
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-22 06:34:45	ID requested
⏵ 1	2025-08-12 03:38:06	announced

10.6019/PXD064192;

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

Kok-Lung Chan
contact affiliation	Associate Professor in Chromosome Dynamics and Stability (Genome Damage and Stability) Chromosome Dynamics and Stability Group Genome Damage and Stability Centre University of Sussex Brighton BN1 9RQ
contact email	KokLung.Chan@sussex.ac.uk
lab head
Umit Aliyaskarova
contact affiliation	Genome Damage & Stability Centre, University of Sussex
contact email	ua65@sussex.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/PXD064192

PRIDE project URI

• PRIDE
  1. PXD064192
     1. Label: PRIDE project
     2. Name: Centromere protection requires strict mitotic inactivation of the Bloom syndrome helicase complex