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Etoposide mechanism of action and poisons on TOP2. The normal catalytic activity of TOP2 creates and reseals the DSB, which involves three steps: TOP2 and DNA binding, TOP2 cleavages DNA double strands, and TOP2 reseal the transient cleaved DNA. Etoposide inhibits TOP2 by stabilizing the TOP2cc. If the trapped TOP2cc can not be adequately repaired, the TDP2 or nuclease will remove the TOP2 from the complex, leading to a persistent and irreversible double-strand DNA break.
