PXD063556

PXD063556 is an original dataset announced via ProteomeXchange.

Title	ARID1A recruits non-homologous end joining factors to DNA breaks induced by G4 ligands
Description	ARID1A is a subunit of the BAF chromatin remodelling complex that is frequently mutated in cancer. However, it is challenging to predict how ARID1A loss might impact on responses to cancer therapies because it participates in many different cellular pathways. G quadruplex (G4) binding ligands, such as pyridostatin, have shown anticancer effects, but the pathways and genetic determinants involved in the response to G4 ligands are still not fully understood. Here, we show that ARID1A deficient cells are selectively sensitive to G4 binding ligands when compared with isogenic controls. Sensitivity to G4 ligands was apparent in both ovarian clear cell and colorectal cancer cell line models, and in vivo studies suggest that G4 ligands might hold promise for treating ARID1A deficient cancers. While we find that ARID1A loss impacts on the transcriptional response to pyridostatin, we find that the influence of ARID1A on pyridostatin-mediated toxicity is driven by the DNA repair response to topoisomerase activity. Specifically, we find that ARID1A deficient cells are unable to efficiently accumulate nonhomologous end joining proteins onto chromatin following exposure to pyridostatin, providing mechanistic insights into their impaired survival. These data uncover a role for ARID1A in the cellular response to G4 ligands, and link chromatin remodelling to G4 ligand-induced DNA damage responses and genome instability.
HostingRepository	PRIDE
AnnounceDate	2025-08-15
AnnouncementXML	Submission_2025-08-15_14:35:18.624.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Graeme Benstead-Hume
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-02 05:54:42	ID requested
⏵ 1	2025-08-15 14:35:19	announced

Dataset with its publication pending

submitter keyword: G4 ligands, ARID1A

Jessica Downs
contact affiliation	ICR
contact email	karen.lane@icr.ac.uk
lab head
Graeme Benstead-Hume
contact affiliation	ICR
contact email	ghume@icr.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD063556
     1. Label: PRIDE project
     2. Name: ARID1A recruits non-homologous end joining factors to DNA breaks induced by G4 ligands