Small molecule inhibitors uncover synthetic genetic interactions of human flap endonuclease 1 (FEN1) with DNA damage response genes
Fig 4
Sensitivity of MSI cell-lines to FEN1 inhibition is through MRE11A deficiency.
A. Cells down-regulated for MRE11A by shRNA are sensitive to FEN1 inhibitor 1. B. Confirmation that the MSI cell-line HCT-116 is disrupted for the MRN complex. Re-introduction of chromosome 3 (HCT-116 chr3) restores MLH1 without affecting MRE11A protein level. C-F. Down-regulation of FEN1 by siRNA is toxic in MSI cells devoid of MRN complex by clonogenic survival (C) or by measuring proliferation (D-F). 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 G. HCT-116 cells fail to signal for the DNA damage response upon treatment with 1.