What is the mechanism of action of DNA topoisomerase II inhibitors?
['DNA topoisomerase II inhibitors are a major class of cancer chemotherapeutics, which are thought to eliminate cancer cells by inducing DNA double-strand breaks.', 'We show that anthracyclines promote histone eviction irrespective of their ability to induce DNA double-strand breaks. The histone variant H2AX, which is a key component of the DNA damage response, is also evicted by anthracyclines, and H2AX eviction is associated with attenuated DNA repair.', 'Induction of apoptotic cell death by DNA topoisomerase II inhibitors', 'The results we have obtained clearly indicate that topoisomerase II poisons induce cell death by apoptosis.', 'Histone eviction deregulates the transcriptome in cancer cells', 'We define a novel mechanism of action of anthracycline anticancer drugs doxorubicin and daunorubicin on chromatin biology, with important consequences for DNA damage responses, epigenetics, transcription']
['DNA topoisomerase II inhibitors eliminate cancer cells by causing DNA double-strand breaks, finally leading to apoptotic cell death. Moreover, drug-induced histone eviction was also shown to be associated with attenuated DNA repair, epigenetic changes and transcpription deregulation.']
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