Antitumour drugs impede DNA uncoiling by topoisomerase I

  title={Antitumour drugs impede DNA uncoiling by topoisomerase I},
  author={Daniel A. Koster and Komaraiah Palle and Elisa S. M. Bot and Mary-Ann Bjornsti and Nynke H Dekker},
Increasing the ability of chemotherapeutic drugs to kill cancer cells is often hampered by a limited understanding of their mechanism of action. Camptothecins, such as topotecan, induce cell death by poisoning DNA topoisomerase I, an enzyme capable of removing DNA supercoils. Topotecan is thought to stabilize a covalent topoisomerase–DNA complex, rendering it an obstacle to DNA replication forks. Here we use single-molecule nanomanipulation to monitor the dynamics of human topoisomerase I in… CONTINUE READING