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DNA Topoisomerases as Targets for the Chemotherapeutic Treatment of Cancer

  • Chapter
Checkpoint Responses in Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development• ((CDD&D))

Abstract

DNA topoisomerases are ubiquitous enzymes that play important roles in a variety of critical nuclear processes. These enzymes control the topological structure of DNA in the cell, regulate under- and overwinding of the double helix, and remove knots and tangles from the genetic material. In order to perform their critical cellular functions, topoisomerases generate DNA strand breaks as requisite intermediates in their catalytic cycles. Consequently, while these enzymes are essential to cell survival, they also have the potential to fragment the genome. The DNA cleavage activity of topoisomerases has been exploited to generate some of the most important drugs currently used to treat human malignancies. This article will familiarize the reader with many aspects of topoisomerase enzymology and cell biology, their interactions with anticancer drugs, and the cellular consequences of topoisomerase-mediated DNA strand breaks. It also will discuss the checkpoint functions and repair pathways that are triggered in response to topoisomerase-generated DNA damage.

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  1. Ryan P. Bender
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  2. Neil Osheroff
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  1. Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY

    Wei Dai PhD

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Bender, R.P., Osheroff, N. (2008). DNA Topoisomerases as Targets for the Chemotherapeutic Treatment of Cancer. In: Dai, W. (eds) Checkpoint Responses in Cancer Therapy. Cancer Drug Discovery and Development•. Humana Press. https://doi.org/10.1007/978-1-59745-274-8_3

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