Figure 1. Function of Tdp1.
Topoisomerase 1 (Top1) excision by tyrosyl DNA phosphodiesterase 1 (Tdp1) requires prior proteolysis (41) or denaturation (21) of Top1 to expose the phosphotyrosyl bond to be attacked. Tdp1 generates a 3′-phosphate DNA end, which is hydrolyzed by polynucleotide kinase phosphatase (PNKP). PNKP also catalyzes the phosphorylation of the 5′ end of the DNA. Tdp1 and PNKP are part of the XRCC1 complex (shown at the bottom) (2,7).