Figure 3. Cells expressing spliceosome mutations confer sensitivity to ATR inhibitors.

(A) HeLa cells stably expressing either U2AF1^WT or U2AF1^S34F were treated with either ATMi or ATRi (5 μM) for 48h. Levels of indicated proteins were analyzed by western blot. (B) HeLa cells stably expressing either U2AF1^WT or U2AF1^S34F were either treated with indicated ATMi or ATRi for 4 days. Relative percent of cell survival was measured by CellTiter-Glo Solution. ***, p≤0.001. (C) U2AF1^WT or U2AF1^S34F expression in OCI-AML3 cells were induced by addition of doxycycline (250 ng/mL) for 48h. Cells were then treated with either DMSO or indicated ATRi doses for 5 days. Cell growth was measured by CellTiter96^®AQueous One Solution. **, p≤0.01, ***, p≤0.001. (D) HeLa cells stably expressing either wild type or different mutants of U2AF1 were treated with ATRi (5 μM) for 48h. Levels of indicated proteins were analyzed by western blot. (E) HeLa cells stably expressing either wild type or P95H mutant of SRSF2 were treated with DMSO or ATRi (5 μM) for 48h. The levels of indicated proteins were analyzed by western blot.