DNA topoisomerases play important roles in DNA replication and in supercoiling . These enzymes are also the targets for certain anticancer drugs (see the introduction to this chapter). Eric Nelson and his colleagues studied m-AMSA, one of the anticancer compounds that acts on topoisomerase (E. M. Nelson, K. M. Tewey, and L. F. Liu. 1984. Proceedings of the National Academy of Sciences of the United States of America 81:1361–1365). They found that m-AMSA stabilizes an intermediate produced in the course of topoisomerase action. The intermediate consists of topoisomerase bound to the broken ends of the DNA. Breaks in DNA that are produced by anticancer compounds such as m-AMSA inhibit the replication of the cellular DNA and thus stop cancer cells from proliferating. Explain how m-AMSA and other anticancer agents that target topoisomerase enzymes taking part in replication might lead to DNA breaks and chromosome rearrangements.

Human Anatomy & Physiology (11th Edition)
11th Edition
ISBN:9780134580999
Author:Elaine N. Marieb, Katja N. Hoehn
Publisher:Elaine N. Marieb, Katja N. Hoehn
Chapter1: The Human Body: An Orientation
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DNA topoisomerases play important roles in DNA replication and in supercoiling . These enzymes are also the targets for certain anticancer drugs (see the introduction to this chapter). Eric Nelson and his colleagues studied m-AMSA, one of the anticancer compounds that acts on topoisomerase (E. M. Nelson, K. M. Tewey, and L. F. Liu. 1984. Proceedings of the National Academy of Sciences of the United States of America 81:1361–1365). They found that m-AMSA stabilizes an intermediate produced in the course of topoisomerase action. The intermediate consists of topoisomerase bound to the broken ends of the DNA. Breaks in DNA that are produced by anticancer compounds such as m-AMSA inhibit the replication of the cellular DNA and thus stop cancer cells from proliferating. Explain how m-AMSA and other anticancer agents that target topoisomerase enzymes taking part in replication might lead to DNA breaks and chromosome rearrangements.

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