Tyrosyl-DNA Phosphodiesterase I Processing of Topoisomerase II-DNA Covalent Complexes is Dependent on Etoposide Stabilization and Tyrosyl-DNA Phosphodiesterase I N-terminal Domain

Tyrosyl-DNA phosphodiesterase I (Tdp1) hydrolyzes 3'- and 5'-phosphodiester linked DNA-adducts, including Topoisomerase I- and II-DNA covalent complexes (Topo1cc and Topo2cc). Utilizing the model organism Saccharomyces cerevisiae, which only expresses Tdp1 and does not contain TDP2 orthologs or activity, we investigated the conditions under which Tdp1 processes Topo2(peptide)cc in cells and examined the role of the Tdp1 N-terminal domain in resolving Topo2(peptide)cc. We replaced the transcripti