Fig. 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” include: DNA damage substrates (e.g. genome embedded ribonucleotides—red, alkylated DNA damage including 1,N6-ethenoadenine—orange, and abasic sites—purple), dietary supplements (e.g. Genistein and Epigallocatechin gallate, EGCG, chemotherapeutics (e.g. Doxorubicin and Etoposide), and various environmental toxicants