Targeted sequencing upon introduction of Cas9-N863A-induced DSBs at these sites (i) confirmed the robust formation of TDs at breaks with 3′ ssDNA in human cells (34.4% and 68.7% of the mutagenic events for sgRNAs L1 + R1 and L2 + R2, respectively) (Figs. 3f and S6b), (ii) revealed that those TDs have a strong resemblance with the ones found in AML patients (Fig. 3g)2, and (iii) provided evidence for evolutionary conservation of the role of the Shieldin-complex in TD formation, as knocking-out REV7 drastically decreased the amount of TDs (Fig. 3f). Here, MAD2L2 is linked to acute myeloid leukemia.