ARID1A stabilizes non-homologous end joining factors at DNA breaks induced by the G4 ligand pyridostatin.

ABSTRACT: ARID1A, a subunit of the BAF chromatin remodeler, is frequently mutated in cancer. Predicting how ARID1A loss impacts cancer therapy response is challenging because it influences many cellular pathways. G quadruplex (G4) binding ligands, such as pyridostatin, show anticancer effects, but the genetic determinants influencing the response to G4 ligands are not fully understood. Here, we show that ARID1A-deficient cells are selectively sensitive to pyridostatin compared to isogenic controls. This was apparent in ovarian and colorectal cancer cell line models, and in vivo studies suggest that G4 ligands hold promise for ARID1A-deficient cancers. While ARID1A modulates pyridostatin-induced transcriptional responses, we show that toxicity in ARID1A-deficient cells arises from the defective repai

SUBMITTER: Simoes-Sousa S 

PROVIDER: S-EPMC12457572 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature