Figure 2: Topoisomerase-2 Cleavage Ligation Equilibrium and Topoisomerase Poisons.
A. TOP2 Catalytic cycle. TOP2 binding G-segment DNA (Left). TOP2 cleaves DNA generating a double strand break of the G-segment DNA and the reaction intermediate is a TOP2-DPC (right). The presence of TOP2 “poisons” shifts the catalytic cycle equilibrium to favor a trapped DNA complex. B. Examples of the chemical structures of Topoisomerases “poisons” to include: DNA damage substrates, dietary supplements, chemotherapeutics, and environmental toxicants.