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Nucleic Acids Research Advance Access originally published online on November 28, 2008
Nucleic Acids Research 2009 37(3):738-748; doi:10.1093/nar/gkn937
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Nucleic Acids Research, 2009, Vol. 37, No. 3 738-748
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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The DNA cleavage reaction of topoisomerase II: wolf in sheep's clothing

Joseph E. Deweese1 and Neil Osheroff1,2,*

1Department of Biochemistry and 2Department of Medicine (Hematology/Oncology), Vanderbilt University School of Medicine, Nashville, TN 37232-0146 USA

*To whom correspondence should be addressed. Tel: +1 615 322 4338; Fax: +1 615 343 1166; Email: neil.osheroff{at}vanderbilt.edu

Received October 7, 2008. Revised October 31, 2008. Accepted November 5, 2008.

Topoisomerase II is an essential enzyme that is required for virtually every process that requires movement of DNA within the nucleus or the opening of the double helix. This enzyme helps to regulate DNA under- and overwinding and removes knots and tangles from the genetic material. In order to carry out its critical physiological functions, topoisomerase II generates transient double-stranded breaks in DNA. Consequently, while necessary for cell survival, the enzyme also has the capacity to fragment the genome. The DNA cleavage/ligation reaction of topoisomerase II is the target for some of the most successful anticancer drugs currently in clinical use. However, this same reaction also is believed to trigger chromosomal translocations that are associated with specific types of leukemia. This article will familiarize the reader with the DNA cleavage/ligation reaction of topoisomerase II and other aspects of its catalytic cycle. In addition, it will discuss the interaction of the enzyme with anticancer drugs and the mechanisms by which these agents increase levels of topoisomerase II-generated DNA strand breaks. Finally, it will describe dietary and environmental agents that enhance DNA cleavage mediated by the enzyme.


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