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. Author manuscript; available in PMC: 2015 Jul 1.
Published in final edited form as: DNA Repair (Amst). 2014 May 22;19:114–129. doi: 10.1016/j.dnarep.2014.03.020

Fig. 2.

Fig. 2

Tyrosyl-phosphodiesterase vs endonuclease pathways for the removal of irreversible topoisomerase cleavage complexes: (A) Top1; (B) Top2. TDP1 and TDP2 (yellow highlights) hydrolyze the tyrosyl-DNA links following proteolysis and/or denaturation of Top1 or Top2. The alternative endonuclease pathways shown in green remove the DNA segment covalently attached to topoisomerases. For Top1, they include XPF-ERCC1 [29,55], Mre11-Rad50-Nibrin/Nbs1 (MRN) [148], SLX4 [161] and CtIP [149,150,162]. For Top2, they include MRN and CtIP [reviewed in [140]]. Double-arrows and orange text indicate the pathways that finalize DNA repair. In the case of Top1 (A), homologous recombination (HR including the BRCA proteins) is critical for repairing the double-strand ends generated by replication run-off [102]. For Top2 (B), end-joining (EJ) with Ku and ligase IV are essential downstream from TDP2 [27,131,132] whereas HR is linked to the endonuclease pathway [140].