PXD068487

PXD068487 is an original dataset announced via ProteomeXchange.

Title	SILAC-iPOND analysis of WT vs ATRX KO eHAP cells ± HU
Description	Mutations in the ATRX chromatin remodeller predispose to a developmental genetic disorder and cancer, but how ATRX safeguards genome and telomere stability remains unresolved. Here, we uncover critical dependencies for the CTC1-STN1-TEN1 (CST) complex and RAD9A-HUS1-RAD1 (9-1-1) clamp in ATRX deficient cells. ATRX:CST synthetic lethality manifests following accumulation of telomeric G-rich ssDNA, which results in telomere loss and cell death. Conversely, we attribute ATRX:9-1-1 synthetic lethality to genome-wide ssDNA lesions, which compromise DNA replication. We further show that ATRX suppresses DNA damage during replication stress by counteracting the activity of the FAM111A protease. We demonstrate that roles of ATRX in telomere maintenance and replication are genetically separable, requiring its ATPase activity and PIP-box, respectively. We also show that such roles protecting genome stability are largely independent of the ATRX-DAXX interaction. Collectively, our data show that functions of ATRX in suppressing toxic ssDNA lesions are context-dependent and are key to global DNA replication and telomere integrity.
HostingRepository	PRIDE
AnnounceDate	2026-05-19
AnnouncementXML	Submission_2026-05-19_04:02:31.432.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sandra Segura-Bayona
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-18 06:22:22	ID requested
⏵ 1	2026-05-19 04:02:31	announced

Dataset with its publication pending

submitter keyword: None

Simon Boulton
contact affiliation	Simon J. Boulton FMedSci FRS Principal Group Leader The Francis Crick Institute Midland Road London, NW1 1AT, UK.
contact email	simon.boulton@crick.ac.uk
lab head
Sandra Segura-Bayona
contact affiliation	The Francis Crick Institute
contact email	sandra.segura-bayona@crick.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/2026/05/PXD068487

PRIDE project URI

• PRIDE
  1. PXD068487
     1. Label: PRIDE project
     2. Name: SILAC-iPOND analysis of WT vs ATRX KO eHAP cells ± HU