RAD18-deficient cells are hypersensitive to DNA cross-linking agents. (A-B) RAD18-deficient and wild-type cells were plated into 6-well plates, treated with increasing amounts of MMC (A) or cisplatin (B), and allowed to grow for 6 days. Crystal violet survival assays show that RAD18-deficient cells are hypersensitive to both MMC and cisplatin. (C) RAD18, FANCD2, luciferase, or RAD18 and FANCD2 were depleted from H1299 cells by siRNA transfection and plated for cell survival assays. Single knockdown of RAD18 or FANCD2 results in hypersensitivity to MMC, whereas double knockdown of RAD18 and FANCD2 reveals an epistatic relationship.