Hervé Jacquiau, Ph.D. is a co-author of this chapter which initially appeared in DNA Topoisomerases in Cancer Therapy: Present and Future. Eukaryotic DNA topoisomerase I (Topl) is a monomeric enzyme that catalyses the relaxation of positively and negatively supercoiled DNA. The nuclear enzyme, encoded by the TOP 1 gene, is highly conserved in terms of reaction mechanism, structure and sensitivity to anticancer agents such as the camptothecins. As with other ON A topoisomerases, Top I 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 ToplDNA intermediate, in which the active site tyrosine of Top I is linked to a 3′ phosphoryl DNA end. This distinguishes type IB enzymes from other DNA topoisomerases, which form a 5′ phosphotyrosyl linkage.
