DNA damage hotspots for the Top2i "ICRF193"

In our project we are using the Top2 inhibitor, ICRF-193, in order to induce damage in NIH3T3 MEFs. We report the high-throughput identification of genomic hotspots for damage induction by ICRF-193, using γH2AX as a marker. We find that ICRF-193 primarily induces damage in repetitive sequences, which are known to reside in regions of heterochromatin, with a very small portion of damaged sites residing in regions of active genes in euchromatin. Overall, this study provides evidence that catalytic inhibition of Top2 enzymes by ICRF-193, leads to induction of damage in the nuclear sub-compartments of heterochromatin. Examination of genomic hotspots for damage induction by ICRF-193, using γH2AX as a marker