Background
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.
References
[1] Cortez, D. et al. (2001) Science 294, 1713-1716.
[2] Itakura, E. et al. (2004) Biochem. Biophys. Res. Commun. 323, 1197-1202.
[3] Zou, L. and Elledge, S.J. (2003) Science 300, 1542-1548.
[4] Yang, X.H. and Zou, L. (2006) Methods Enzymol. 409, 118-131.
[5] Ball, H.L. et al. (2007) Mol Cell Biol 27, 3367-77.
