Supplementary Figure 4: DNA-repair-inhibitor and DNA-damaging-agent sensitivity in cells deficient in Krebs-cycle enzymes.

(a) Clonogenic survival assay in HEK293FT shSDHB clone 1 ( + doxycycline), HEK293FT shFH clone 1 ( + doxycycline) and HEK293FT shCTRL ( + doxycycline) after treatment with the indicated doses of ionizing radiation. Dose enhancement ratio at 0.1 survival is indicated. (b, c, and d) Clonogenic survival assay in HEK293FT shSDHB clone 1 + doxycycline, HEK293FT shFH clone 1 + doxycycline, and HEK293FT shCTRL + doxycycline with the indicated doses of (b) mitomycin C (c) cisplatin and (d) etoposide. (e and f) Clonogenic survival assay with the indicated doses of (e) Olaparib and (f) BMN-673 for YUNK1 cells also treated or not with 30 µM or 60 µM of dimethyl fumarate, as indicated, or with doxycycline to induce FH knockdown. (g and h) Clonogenic survival assay with the indicated doses of (g) Olaparib and (h) BMN-673 for YUNK1 cells also treated or not with 2 mM succinate. (i) Clonogenic survival assay in YUNK1 cells with constitutive shRNA knockdown of FH and SDHB in response to BMN-673. (j) Clonogenic survival assay of cell lines of renal origin treated with indicated doses of mitomycin C. (k-l) Clonogenic survival assay in response to BMN-673 in HeLa cells also treated or not with (k) 2 mM succinate or (l) 1 mM monoethyl-fumarate or 60 µM dimethyl-fumarate. For all panel n = 3, dots represent mean + /- SEM.