In response to genomic stress, the ATR interacting protein binds and is phosphorylated by the DNA damage-and checkpoint-activated kinase ATR. Both ATR and ATRIP are integral for checkpoint signaling and are critical in the DNA repair response. Direct interaction between ATRIP and replication protein A at RPA-coated, single-stranded DNA results in the recruitment of phosphorylated ATR/ATRIP to stalled replication forks and sites of DNA damage. ATR/ATRIP coordinate DNA repair and cell cycle progression in conjunction with key regulatory proteins, such as Rad17 and the 9-1-1 complex. ATR associated with ATRIP can also be stimulated by topoisomerase II binding protein, suggesting that ATRIP may regulate both ATR localization and activity.
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