Fig. 4From: Participation of the ATR/CHK1 pathway in replicative stress targeted therapy of high-grade ovarian cancerParticipation of ATR in maintenance of genome stability. DNA double strand breaks or replication stress induce an ATR protein response. ATR is recruited to regions of ssDNA replication protein A (RPA) through its partner, ATR-interacting protein (ATRIP). Subsequently, RAD9–RAD1-hus1 (9-1-1 complex) and DNA topoisomerase 2 binding protein 1 (TOPBP1) are incorporated, leading to ATR activation. ATR–ATRIP recruitment results in CHK1 activation. This process is mediated by Claspin, Timeless and Tipin, which form a complex at replication forks. In the event of large areas of DNA damage or no repair, the replication fork stops, origin suppression occurs and the cell cycle is stopped. ATR/CHK1 blockade prevents DNA damage-induced cell-cycle arrest, resulting in inappropriate entry into mitosis, chromosome aberrations, unequal partitioning of the genome, and apoptosisBack to article page