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Essential Functions of Topoisomerase IIIα in the Nucleus and Mitochondria

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DNA Topoisomerases and Cancer

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

Abstract

Topoisomerase IIIα (Top3α) is the essential eukaryotic member of the type IA class of topoisomerases. The absence of Top3α leads to embryonic lethality in fruit flies and mice. One of the main roles of the enzyme in the nucleus appears to be prevention of aberrant recombination by resolving double Holliday junction structures into non-crossover products; this role requires the formation of a complex with functional Bloom’s helicase as well as the structural Rmi proteins. While the exact stoichiometry and mechanism of action of the complex is not yet known, we present two models for how the resolution may occur. In addition, Top3α appears to play a key role in the mitochondria, where it may assist in the segregation of daughter chromosomes; a model for the role of Top3α in late replication intermediates is also presented. In this chapter, we outline the discovery, known functions, and future implications of Top3α in the cell.

These authors contributed equally to this work.

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Authors and Affiliations

  1. Department of Biochemistry, Duke University Medical Center, Durham, NC, USA

    Stefanie Hartman Chen & Jianhong Wu

  2. Department of Biochemistry, Duke University Medical Center, Durham, NC, 27710, USA

    Tao-shih Hsieh

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  1. Stefanie Hartman Chen
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  2. Jianhong Wu
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  3. Tao-shih Hsieh
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Correspondence to Tao-shih Hsieh .

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Editors and Affiliations

  1. Laboratory of Molecular Pharmacology, National Institutes of Health Laboratory of Molecular Pharmacology, Bethesda, Maryland, USA

    Yves Pommier

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Chen, S.H., Wu, J., Hsieh, Ts. (2012). Essential Functions of Topoisomerase IIIα in the Nucleus and Mitochondria. In: Pommier, Y. (eds) DNA Topoisomerases and Cancer. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0323-4_5

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  • DOI: https://doi.org/10.1007/978-1-4614-0323-4_5

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