Figure 1: Chemical genetic screen reveals MEK inhibitor sensitivity of ATM-depleted cells.

(a) Gene–drug interaction screen in AALE cells (see Methods). Synthetic lethal drug interactions are sorted based on Z-score for each indicated tumour suppressor. The interactions between ATM and AZD7762 (green circle) and PD0325901 (red circle) are indicated with black arrows. (b) Dose–response curve with the Chk1/2 inhibitor AZD7762. AALE cells were infected as indicated and treated with the drug for 3 days. Displayed is the relative viability that is calculated by normalizing the raw CellTiter-Glo data to the vehicle (DMSO) treated controls. Error bars indicate s.d. (n=3). (c) Colony formation of AALE cells infected with ATM shRNA or control virus and treated with PD0325901 for 10 days. Shown is a representative example (n=3). Numbers in the bottom right corners indicate quantification relative to DMSO-treated samples. (d) Growth curves of indicated AALE cell lines treated with PD0325901 (1 μM). Cells were counted and passaged every 3 days and seeded at equal densities. ^**P<0.01, two-sided t-test (n=2 biological replicates). (e) Western blot analysis of AALE cells infected with ATM knockdown vectors. (f) Cell viability of AALE cells infected with indicated vectors and treated with PD0325901 for 3 days. Data are normalized to vehicle (DMSO). Indicated are s.d.’s. ^****P<0.0001, two-sided t-test (n=3). (g) Relative cell viability of AALE cells stably infected with ATM shRNA or control viruses and treated with trametinib for 3 days. Data are normalized to vehicle (DMSO). Error bars indicate s.d.’s (n=3).