REV7 associates with ATRIP and inhibits ATR kinase activity.

ABSTRACT: Ataxia-telangiectasia mutated and RAD3-related (ATR) and its partner ATR-interacting protein (ATRIP) function as a critical proximal sensor and transducer of the DNA damage response (DDR). Several ATR substrates, including p53 and CHK1, are crucial for the coordination of cell cycle phase transitions, transcription, and DNA repair when cells sustain DNA damage. While much is known about ATR activation mechanisms, it is less clear how ATR signaling is negatively regulated in cells. Here, we identify the DNA repair protein REV7 as a novel direct binding partner of ATRIP. We define a REV7-interaction motif in ATRIP, which, when mutated, abrogates the REV7-ATRIP interaction in vitro and in intact cells. Using in vitro kinase assays, we show that REV7 inhibits ATR-mediated phosphorylation of it

SUBMITTER: Biller M 

PROVIDER: S-EPMC12820532 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature