We also report here a higher proportion of residual IR-induced γH2AX and 53BP1 foci upon pharmacologic inhibition of Polθ linked to increased formation of IR-induced micronuclei, which strongly suggests that the mechanism whereby our Polθ inhibitors radiosensitize cancer cells is by an impairment in DSB repair, which leads to lethal chromosomal rearrangements (32). This evidence concerns the gene TP53BP1 and cancer.