Figure 1.

Comparison of main features of AsiDNA and Olaparib activity on DNA repair. I: Activity of the inhibitors AsiDNA (left) and olaparib (right). AsiDNA is a short modified DNA mimicking double-strand break. It binds DNA-PK and PARP enzymes and activates their kinase and polymerase activity leading to modification of a large number of cellular proteins including pan nuclear γ-H2AX protein and poly-ADP-Ribose (PAR) (A). These modifications occur in absence of DNA damage as revealed by 53BP1 foci and comet assay (C) (12). In contrast, olaparib inhibits PARP polymerase activity and induces increase of DNA damage (13) (B,C) probably through inhibition of base excision repair (BER) and increase of replicative stress. II: Drug effect on damage signaling and recruitment of DSB repair proteins after damage. Damages were induced either by γ irradiation or laser (^*). Three DSB repair pathways were monitored: homologous recombination (HR), non-homologous end joining (NHEJ), and micro homology end joining (MHEJ, also called alt-NHEJ). Whereas, olaparib inhibits the formation of foci of XRCC1 and PARP1 (14), it has no effect on formation of radio-induced foci of γ-H2AX, 53BP1, RAD51, and BRCA2 (D,E). In contrast, AsiDNA inhibit recruitment of 53BP1, XRCC4, RAD51, and BRCA2 (15) (F) and do not prevent recruitment of PARP and XRCCI (G).