Topoisomerase Inhibitors
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Topoisomerase I and II Function
- DNA forms positive and negative supercoils (twisted loops) during the cell cycle. Topoisomerases (topo-1 and topo-2) are instrumental in managing these supercoils appropriately.
- Topoisomerase I cleaves and reseals a single strand of DNA to remove negative supercoils one supercoil at a time (think: topoisomerase one – one strand).
- Topoisomerase II, cuts both strands of DNA (think: topoisomerase two – two strands). It can flip a positive supercoil into a negative supercoil or adds two negative supercoils to the DNA.
Topotecan, Irinotecan (Topo-I Inhibitors)
- Indicate that topotecan and irinotecan, which are camptothecins, inflict damage through topoisomerase I inhibition – primarily in the S phase of the cell cycle.
Etoposide, Teniposide (Topo-II Inhibitors)
- Show that etoposide and teniposide create damage through topoisomerase II inhibition – primarily in the late S and early G2 phases.