DNA-PKcs inhibitor Nu7026 induces mitotic slippage after irradiation, related to Figure 7 and Figure S5.
Time-lapse imaging of MCF7-FUCCI cells treated with DMSO or Nu7026 (3 μM) following 6 Gy irradiation or not. Cells were treated with DMSO or Nu7026 (3 μM) for 1 h, irradiated with 0 Gy or 6 Gy and then images were taken at 2 h intervals. Following 0 Gy, most of the cells underwent normal mitosis in which parent cells divided into two separated daughter cells approximately every 24 h in the presence or absence of Nu7026. Following 6 Gy, though some of the surviving cells treated with DMSO recovered from irradiation after a few cell cycles, others lost the capability for cell division and accumulate as flattened and enlarged cells displaying characteristic senescent morphology. However, many surviving cells with Nu7026 treatment entered the cell cycle but failed to complete cytokinesis and yielded binucleated cells, which adopted a senescent phenotype over time. Most cells with senescent morphology terminally arrested while expressing mCherry-hCdt1 (red), representing G1 cell cycle stage. Scale bar = 100 μm.