REV7 associates with ATRIP and FAM35A

REV7 is a remarkably multi-faceted protein with important and separable roles in multiple genome maintenance pathways including Trans-Lesion Synthesis, the Fanconi Anemia pathway, as well as p53 signaling and Double Stranded Break resection. To investigate novel functions and pathways involving REV7, we performed mass-spectrometry analysis and identified proteins associated with REV7. We discovered two novel factors: the ATR-ATRIP complex and FAM35A. The REV7-FAM35A interaction was reported in a previous paper. Here, we identified the ATR-binding partner and activator ATRIP as a new REV7-associated protein. Through a comprehensive series of in vitro biochemical studies and cell-based assays we demonstrate that ATRIP is a direct binding partner of REV7, and that REV7-ATRIP interactions are critical for negative regulation of ATR activity. Our findings establish a new mechanism for negative regulation of ATR by the DNA repair protein REV7.