Fig. 4

DNA-PK inhibitors stimulate homology-directed repair at the p53 locus. a Outline of experimental approach. b Position of target sites and partial sequence of oligonucleotides used as repair templates for p53 exons 5 and 7. A schematic representation of the murine p53 locus is shown with the locations of sgp53-1 and sgp53-3. The sequence of the donor templates for HDR (sgp53-1; 105 nucleotides, sgp53-3; 106 nucleotides) are indicated with red nucleotides denoting missense mutations and a dash indicating a frameshift mutation leading to a premature stop codon (in bold). c Fold stimulation of HDR at the sgp53-1 and sgp53-3 sites by NU7441 (2 μM) or KU-0060648 (250 nM). Results are shown as the fraction of all retrieved mutated sequences that correspond to HDR events in the presence of the DNA-PK inhibitors relative to vehicle. N = 4; error bars represent S.D. Results are from biological replicates performed in technical duplicates. Significance (relative to vehicle) was calculated using the Student’s t-test: *p ≤0.05; **p ≤0.01; ns, not significant