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

Figure 3. Tubulin binders inhibit HDR.

Figure 3

(A) The tubulin binders combretastatin A4 (CA4), taxol, and vinblastine inhibit gene conversion in the U2OS-DR-GFP cells. (B) CA4, taxol, and vinblastine inhibit formation of Rad51 foci in CHO AA8 cells at 2 hours after 3 Gy. (C) Colocalization of Rad51 and γH2AX foci shows that Rad51 foci are induced at DSBs and that taxol reduces Rad51 accumulation at DSBs. Scale bars: 10 μm. Insets show higher magnification of selected γH2AX foci. (D) CA4, taxol, and vinblastine increase the sensitivity of CHO AA8 cells to chlorambucil. (E) Taxol and vinblastine increase chlorambucil sensitivity of CHO mutant cells defective in nucleotide excision repair (UV5, UV20, and UV41) and base excision/single-strand break repair (EM9), but do not increase chlorambucil sensitivity of irs1SF cells defective in HDR. UV5, irs1SF, UV41, UV20, and EM9 cells have mutations in the XPD, XRCC3, XPF, ERCC1, and XRCC1 genes, respectively. Shown are means ± SDs from n ≥ 3 experiments (A, B, and D) and means ± SDs from n > 2 experiments (E; ranges are shown for points with 2 replicates). Significance analysis: 1-way ANOVA (A and B) and 2-way ANOVA (D and E). Drug-treated samples were compared with the solvent controls. **P < 0.01, ***P < 0.001, ****P < 0.0001.