PXD059007

PXD059007 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	PHOSPHORYLATION-DEPENDENT ASSOCIATION OF WRN WITH RPA IS REQUIRED FOR RECOVERY OF REPLICATION FORKS STALLED AT SECONDARY DNA STRUCTURES
Description	The WRN protein mutated in the premature aging disorder Werner syndrome is vital for metabolism of perturbed replication forks. Replication Protein A (RPA) robustly enhances WRN helicase activity in specific cases when tested in vitro. However, the significance of RPA-binding to WRN in vivo has remained largely unexplored. We identified several conserved phosphorylation sites in the acidic domain of WRN targeted by Casein Kinase 2 (CK2). These sites are crucial for WRN-RPA interaction in vitro and in human cells. Using the CK2-unphosphorylatable WRN mutant lacking the ability to bind RPA, we determined that the WRN-RPA complex plays a critical role in fork recovery after replication stress whereas is not necessary for the processing of replication forks or preventing DNA damage when forks stall or collapse. RPA-binding by WRN and its helicase activity are crucial for countering the persistence of G4 structures after fork stalling. Absence of WRN-RPA binding hampers fork recovery, causing single-strand DNA gaps, enlarged by MRE11, and triggering MUS81-dependent double-strand breaks which requires efficient repair by RAD51 to prevent excessive DNA damage.
HostingRepository	MassIVE
AnnounceDate	2024-12-18
AnnouncementXML	Submission_2024-12-18_11:31:23.430.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	FEDERICA FRATINI
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Phospho
Instrument	Orbitrap Fusion

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-18 11:29:17	ID requested
⏵ 1	2024-12-18 11:31:23	announced

Publication List

no publication

no publication

Keyword List

submitter keyword: WERNER PHOSPHOSITES

submitter keyword: WERNER PHOSPHOSITES

Contact List

FEDERICA FRATINI
contact affiliation	ISS
contact email	federica.fratini@iss.it
lab head
FEDERICA FRATINI
contact affiliation	ISS
contact email	federica.fratini@iss.it
dataset submitter

Full Dataset Link List

MassIVE dataset URI
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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.ucsd.edu/v08/MSV000095749/