PXD061463

PXD061463 is an original dataset announced via ProteomeXchange.

Title	USP37 prevents unscheduled replisome unloading through MCM complex deubiquitination
Description	The CMG helicase (CDC45-MCM2-7-GINS) unwinds DNA as a component of eukaryotic replisomes. Replisome (dis)assembly is tightly coordinated with cell cycle progression to ensure genome stability. However, factors that prevent premature CMG unloading and replisome disassembly are poorly described. Since disassembly is catalyzed by ubiquitination, deubiquitinases (DUBs) represent attractive candidates for safeguarding against untimely and deleterious CMG unloading. We combined a targeted loss-of-function screen with quantitative, single-cell analysis to identify human USP37 as a key DUB preventing replisome disassembly. We demonstrate that USP37 maintains active replisomes on S-phase chromatin and promotes normal cell cycle progression. Proteomics and biochemical assays revealed USP37 interacts with the CMG complex to deubiquitinate MCM7, antagonizing replisome disassembly. Significantly, USP37 protects normal epithelial cells from oncoprotein-induced replication stress. Our findings reveal USP37 to be critical to the maintenance of replisomes in S-phase and suggest USP37-targeting as a potential strategy for treating malignancies with defective DNA replication control.
HostingRepository	PRIDE
AnnounceDate	2025-05-16
AnnouncementXML	Submission_2025-05-16_12:23:30.993.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Angie Mordant
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-04 09:01:20	ID requested
⏵ 1	2025-05-16 12:23:31	announced

Dataset with its publication pending

submitter keyword: USP37, cell cycle, ubiquitin, DNA replication, replisome

Michael J Emanuele
contact affiliation	Linerberger Comprehensive Cancer Center (LCCC); Department of Pharmacology, University of North Carolina at Chapel Hill
contact email	emanuele@email.unc.edu
lab head
Angie Mordant
contact affiliation	UNC Proteomics Core, Department of Pharmacology, University of North Carolina at Chapel Hill
contact email	angie_mordant@med.unc.edu
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/2025/05/PXD061463

PRIDE project URI

• PRIDE
  1. PXD061463
     1. Label: PRIDE project
     2. Name: USP37 prevents unscheduled replisome unloading through MCM complex deubiquitination