Fig. 4.

Overview of TOP2-DPC resolution. a Variable 5′ DNA termini produced subsequent to (1) protease degradation (2) ZATT-licensed Remodeling of TOP2-DPC. Protease digestion of TOP2 removes TOP2 protein leaving behind a variable length peptide of TOP2 and a 5-phosphotyrosol linkage. Accessibility of the 5′ phosphotyrosyl linkage can also be regulated by remodeling. ZATT binds to and remodels TOP2-DPC promoting 5′ phosphotyrosyl linkage accessibility. b Removal of 5′Y. (Left) Nucleolytic processing mediated by a large complex of DNA repair proteins importantly CtIP, MRN. (Right) Direct Resolution of the 5′ phosphotyrosyl by Tyrosyl–DNA Phosphodiesterases 2 (TDP 2) producing a ligation competent 5′P on DNA