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Yeast as a model system in the analysis of DNA topoisomerase I poisons

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DNA Topoisomerases in Cancer Therapy

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Abstract

Eukaryotic DNA topoisomerase I (Top1) is a monomeric enzyme that catalyses the relaxation of positively and negatively supercoiled DNA (reviewed in Reid et al., 1998; Champoux, 2001; Wang, 2002). The nuclear enzyme, encoded by the TOP1 gene, is highly conserved in terms of reaction mechanism, structure and sensitivity to anticancer agents such as the camptothecins (Redinbo et al., 1999; Fiorani and Bjornsti, 2000; Li and Liu, 2001). As with other DNA topoisomerases, Top1 forms a protein clamp that completely circumscribes duplex DNA. The transient cleavage and religation of a single DNA strand is accompanied by the formation of a covalent Top1-DNA intermediate, in which the active site tyrosine of Top1 is linked to a 3’ phosphoryl DNA end. This distinguishes type IB enzymes from other DNA topoisomerases, which form a 5’ phospho-tyrosyl linkage.

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Abstract

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  1. Department of Molecular Pharmacology, St. Jude Children’s Research Hospital, 332 N. Lauderdale, Memphis, Tennessee, 38105, USA

    Hervé R. Jacquiau & Mary-Ann Bjornsti

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  1. Hervé R. Jacquiau
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  1. Department of Bioengineering Faculty of Engineering, Soka University, 1-236 Tangi-cho, Hachioji, Tokyo, 192-8577, Japan

    Toshiwo Andoh

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Jacquiau, H.R., Bjornsti, MA. (2003). Yeast as a model system in the analysis of DNA topoisomerase I poisons. In: Andoh, T. (eds) DNA Topoisomerases in Cancer Therapy. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0141-1_5

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