AT-rich interactive domain-containing protein 1A (ARID1A (also known as BAF250a))

AT-rich interactive domain-containing protein 1A (ARID1A, BAF250a) is a large, noncatalytic DNA-binding subunit of the ATP-dependent SWI/SNF (BAF) chromatin-remodeling complex that confers target specificity and regulates transcription by altering chromatin structure; it contains an ARID DNA-binding domain that generally binds DNA without strict sequence specificity, large intrinsically disordered regions mediating multiple protein interactions, and can co-regulate steroid receptor–dependent transcription; ARID1A functions as a tumor suppressor and is among the most frequently mutated SWI/SNF components across cancers, with inactivating mutations leading to loss of nuclear protein; it also participates in DNA damage response by being recruited to double-strand breaks through ATR, facilitating end resection and ATR–Chk1 signaling, creating therapeutic vulnerabilities such as synthetic lethality to ATR inhibition

Other names

ARID1ABAF250aSWI1 homologAT-rich interaction domain 1Ap270/ARID domain protein

Synthetic lethality of ATR inhibition in ARID1A-deficient tumors: ATR inhibitor blocks decatenation checkpoint and ATR–Chk1 signaling, leading to mitotic catastrophe in cells reliant on ATR due to ARID1A loss; Targeting hyperactivated PI3K/AKT signaling consequent to ARID1A loss (therapeutic rationale from ARID1A’s repression of PIK3CA/PDK1)