“Yeast as a Model System in the Analysis of DNA Topoisomerase I Poisons”

Hervé Jacquiau, J.D., Ph.D., M.Sc., D.E.A.

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.

Hervé Jacquiau, Ph.D., assists in all aspects of patent practice, including patent prosecution and litigation. His background covers a variety of technologies, particularly biotechnology, bioengineering, biochemistry, molecular biology and microbiology. He received his Ph.D. degree from the University of Cambridge after investigating the genetic and biochemical features responsible for the biodegradation of toxic pollutants.