Small molecule inhibitors uncover synthetic genetic interactions of human flap endonuclease 1 (FEN1) with DNA damage response genes
Fig 6
FEN1 is epistatic with FANCD2 for the repair of olaparib- and cisplatin-induced DNA damage.
A. Olaparib sensitivity of cells disrupted for FEN1, FANCD2 or BRCA2 by shRNA compared to a non-target control. B. Sensitisation of cells to olaparib following treatment with 10 μM 1. C. Epistasis analysis of FEN1 inhibition and FANCD2 depletion following exposure to olaparib. D. Cisplatin sensitivity of cells disrupted for FEN1, XPF and FANCD2 by shRNA compared to a non-target control. E. Sensitisation of cells to cisplatin following treatment with 5 μM 1. F. Epistasis analysis of FEN1 inhibition and FANCD2 depletion following exposure to cisplatin. G-I. Sensitivity of Saccharomyces cerevisiae strains deleted for rad27, pso2, msh2 singularly and in combination either in asynchronous culture (G) or synchronised in S-phase (H-I). In all cases, each data point is the mean of at least 3 individual repeats and the error bars represent the standard error. Significance was determined by student t-test. ns = not significant * p < 0.05. ** p < 0.005.