TDP2 promotes survival following TOP2-induced DSBs.

<p>A. Clonogenic survival of the indicated DT40 cell line; wild-type, <i>TDP2^−/−/−</i> and <i>TDP2^−/−/−</i> complemented with human TDP2 (hTDP2) and catalytic-dead human TDP2 (hTDP2 262A) or empty vector (Empty V); following continuous treatment with the indicated concentrations of doxorubicin (left) or mAMSA (right). Average ± s.e.m. of at least three independent experiments and statistical significance at the highest indicated dose when compared to <i>TDP2^−/−/−</i> cells by Two-way ANOVA with Bonferroni post-test is shown. B. Scheme showing the strategy for targeted deletion of the first three exons of <i>Tdp2</i> in mouse. The wild-type (<i>Tdp2⁺</i>), conditional (<i>Tdp2^{flEx1–3,neo}</i>) and deleted (<i>Tdp2^flΔ</i>) alleles are depicted. The <i>EcoRI-EcoRI</i> fragment of <i>Tdp2</i> was used in the targeting construct. Southern-blot analysis of <i>PstI</i>-digested DNA from wild-type (<i>+/+</i>), heterozygous (<i>+/flΔ</i>) and knock-out (<i>flΔ/flΔ</i>, from now on denoted <i>Tdp2^Δ1–3</i>) mice, using the indicated probe (red line), is shown (bottom right). C. Clonogenic survival of wild-type and <i>Tdp2^Δ1–3</i> transformed MEFs after 3 h acute exposure to the indicated concentrations of etoposide (left) or the indicated dose of γ-irradiation (right). Average ± s.e.m. of three independent experiments and statistical significance by Two-way ANOVA test with Bonferroni post-test is shown. In all figures (*P≤0.05; **P≤0.01; ***P≤0.005).