PXD066219

PXD066219 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	SLFN11 counteracts the RFWD3-PRIMPOL DNA damage tolerance pathway to restrain gapped DNA synthesis in response to replication stress
Description	Schlafen family member 11 (SLFN11) expression sensitizes cells to a spectrum of DNA-damaging chemotherapies. Previous studies have shown that SLFN11 is recruited to stalled replication forks in response to replication stress; however, the role of SLFN11 at stressed replication forks remains unclear. Using single-molecule DNA fiber analysis and super-resolution microscopy to interrogate the dynamics of individual replication forks, we show that SLFN11 acts upon stalled replication forks to suppress efficient fork restart. In the absence of SLFN11 expression, fork restart proceeds through a pathway involving the ubiquitin ligase RFWD3 and the DNA primase-polymerase PRIMPOL to facilitate gapped DNA synthesis. In the absence of SLFN11 expression, this pathway ensures that cells do not accumulate replication-associated DNA damage in response to stalled forks. Collectively, our results provide a mechanistic basis for how SLFN11 can counteract DNA damage tolerance by suppressing the RFWD3-PRIMPOL axis. The deposit includes the mass spectrometry data files generated from this study.
HostingRepository	MassIVE
AnnounceDate	2025-10-23
AnnouncementXML	Submission_2025-10-23_10:50:41.108.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Evgeny Kanshin
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Deamidated; Oxidation; Phospho
Instrument	timsTOF HT; Orbitrap Eclipse

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-16 09:05:30	ID requested
⏵ 1	2025-10-23 10:50:41	announced

Publication List

no publication

no publication

Keyword List

submitter keyword: Schlafen-11, SLFN11, DNA synthesis, fork restart, PRIMPOL, RFWD3, fork-stalling, replication stress, hydroxyurea, DNA damage tolerance, DatasetType:Proteomics

submitter keyword: Schlafen-11, SLFN11, DNA synthesis, fork restart, PRIMPOL, RFWD3, fork-stalling, replication stress, hydroxyurea, DNA damage tolerance, DatasetType:Proteomics

Contact List

Beatrix M Ueberheide
contact affiliation	NYU Langone Grossman School of Medicine
contact email	beatrix.ueberheide@nyulangone.org
lab head
Evgeny Kanshin
contact affiliation	NYU Langone Health
contact email	evgeny.kanshin@nyulangone.org
dataset submitter

Full Dataset Link List

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MassIVE dataset URI

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://massive-ftp.ucsd.edu/v10/MSV000098536/