Fig. 5: SPT chemical inhibition increases PARPi sensitivity of BRCA-1 deficient human cancer cell lines.

a IF for Lamin-A of representative nuclei of breast cancer HCC-1937 cell line cells treated with DMSO or myriocin for 24 h, with quantification of NE invaginations in one representative experiment. Scale bars, 10 μm. DMSO n = 63; myriocin n = 62. b, c Representative survival assay (b) and quantification (c) of HCC-1937 cells after exposure for 24 h to myriocin and/or 72 h exposure to PARPi at the indicated concentrations. After removal of the drugs, cells were let grow for a week before harvest. Cells were stained with methylene blue (b) or counted after trypsinization (c). Quantifications of growth is normalized over the growth without PARPi. Data represents average and SEM for n = 3 independent experiments. Representative survival assay (d) and quantification of uWB1.289 ovarian cancer cell line expressing exogenous BRCA1 (e) or the original BRCA1-deficient uWB1.289 cell line (f) after exposure for 24 h to the indicated concentrations of PARPi and myriocin as described in (b, c). Quantifications of growth is obtained independently for uWB1.289 + BRCA1 and uWB1.289. Data represents average and SEM for n = 5 independent experiments. g Proposed model of how nuclear deformability increases microtubule-dependent DSBs mobility and misrepair, enhancing the sensitivity of BRCA1-deficient cells to PARPi treatment. Source data are provided as a Source Data file. See also Supplementary Fig. 5.