TDP2–Dependent Non-Homologous End-Joining Protects against Topoisomerase II–Induced DNA Breaks and Genome Instability in Cells and In Vivo
Figure 8
Model for the repair of TOP2-induced DSBs.
(a) TDP2-mediated cleavage of the 5′ phosphodiester link between TOP2 peptide and DNA results in 3′ hydroxyl (OH) 5′ phosphste (P) cohesive ends that are easily ligatable by NHEJ resulting in error-free repair. (b) Alternatively, nucleolytic attack on the DNA backbone can also remove the protein adduct from the DSB but genetic information is lost from the ends. Accurate repair of this break would therefore need HR to copy the missing information from the sister chromatid, while NHEJ would result in error-prone repair.