v-Src inhibits the interaction between Rad17 and Rad9 and induces replication fork collapse.

ATR-dependent DNA damage checkpoint is crucial to maintain genomic stability. Recently, we showed that Src family kinases suppress ATR-dependent checkpoint signaling in termination of DNA damage checkpoint. However, the precise molecular mechanism is unclear. Therefore, we examined the role of oncogenic v-Src on ATR-Chk1 signaling. We show that v-Src suppresses thymidine-induced Chk1 phosphorylation and induces replication fork collapse. v-Src inhibits interaction between Rad17 and Rad9 in chromatin fraction. By contrast, v-Src does not inhibit RPA32 phosphorylation, ATR autophosphorylation, or TopBP1-Rad9 interaction. These data suggest that v-Src attenuates ATR-Chk1 signaling through the inhibition of Rad17-Rad9 interaction.