A. Expression of key DDR and RS markers following treatment of TP53-deficient lung cancer cell lines Calu-1, H2250, H1299 and 344SQ with BGB324, VX-970 or their combination (1μM) for 24 h analyzed by western blotting. β-Actin was used as loading control. B. Immunoblots of Calu-1 and H1299 cells treated with BGB324, VX-970, or their combination for indicated durations. Hydroxyurea (0.5mM) was used as a positive control for RS. Changes in RS markers (pCHK1, pRPA32) and DNA damage (γH2Ax) seen as early as 4 h post treatment with BGB324/VX-970 combination. C. Similar increases in DNA damage and RS markers were observed in Calu-1 and H1299 cells treated with BGB324 and another ATR inhibitor, AZD6738. D. 344SQ shCTRL and 344SQ AXL knockdown cells were treated with 0.5μM VX-970 for 4 h or 24 h. Expression of DNA damage and RS markers were analyzed by western blotting. E. Increases in DNA damage and RS markers were not as pronounced in TP53-wildtype cell lines treated with BGB324/VX-970 combination.