Diversity of DNA topoisomerases I and inhibitors

The present review first describes the different type I topoisomerases found in eukaryotic cells: nuclear topoisomerase I (top1), topoisomerase 3 (top3), mitochondrial topoisomerase I and viral topoisomerases I. The second part of the review provides extensive information on the topoisomerase I inhibitors identified to date. These drugs can be grouped in two categories: top 1 poisons and top 1 suppressors. Both inhibit enzyme catalytic activity but top1 poisons trap the top1 catalytic intermediates ('cleavage complexes') while top1 suppressors prevent or reverse top1 cleavage complexes. The molecular interactions of camptothecin with the top1 cleavage complexes are discussed as well as the mechanisms of selective killing of cancer cells. ((C) Society francaise-de biochimie et biologie moleculaire / Elsevier, Paris).