Topoisomerase inhibitors are chemical compounds that block the action of topoisomerases.
- Intercalating drugs are used for cancer chemotherapy because they poison cells that are rapidly dividing, like the cells in a growing tumor
- Action of topoisomerase begins by breaking one of DNA strands
- then they induce a topological change in DNA such as relaxing supercoils or untangling strands
- and finally they reconnect the DNA in its proper form.
- Intercalating drugs block the reconnection step, freezing the topoisomerase after it has broken the DNA.
- This is a problem for a dividing cell: when a replication fork reaches the site, a lethal double-strand break is formed as the replication machinery passes through the damaged DNA.