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. 2018 Oct 29;128(12):5307–5321. doi: 10.1172/JCI87191

Figure 6. Upregulation of HDR by direct stimulation of RAD51 activity or overexpression of RAD51 overcomes dynasore-induced sensitization to chlorambucil.

Figure 6

(A) Stimulation of RAD51 activity by RS-1 overcomes dynasore-induced inhibition of gene conversion in U2OS-DR-GFP cells. Shown are means and SDs from n ≥ 2 experiments. Ranges are shown for points with 2 replicates. (B) CHO AA8 cells are effectively sensitized to chlorambucil by dynasore, and RS-1 (7.5 μM) reverses this dynasore effect. MTS assay: Shown are means ± SDs from n ≥ 2 experiments. Ranges are shown for points with 2 replicates. (C) U2OS cells overexpressing the RAD51-HA construct show increased resistance to chlorambucil. While U2OS cells are effectively sensitized to chlorambucil by dynasore, the effect of dynasore is lost or reduced in cells overexpressing RAD51. MTS assay: Shown are means and SDs from n ≥ 3 experiments. See Supplemental Figure 8A for Western blots showing the overexpression of RAD51 and for the significance analysis. (AC) Significance analysis: ANOVA. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.