OK, this paper actually has massive implications for topoisomerase drug discovery because it challenges a long-standing assumption about TOP2 poisons. Rather than simply trapping the cleavage complex (as etoposide does), the authors propose that their modified epipodophyllotoxin derivative actively dismantles the TOP2β catalytic apparatus, producing an irreversible, religation-defective complex that leads to persistent DNA double-strand breaks. Topoisomerase […]