LIG3 and neoplasm: Although further investigation is required to finally validate the specific binding site on LIG3 and dissect the mechanisms of anti-tumor activity, and integrative multi-omics platforms at different molecular levels might provide valuable insights into the complexity of this biological system [71–77], based on our findings, we could hypothesize that RHM impairs DNA Ligase III activity by binding to PCG of DBD, thus hampering DNA damage recognition, repair and chromosome translocations (Fig. 6).