DNA Topoisomerases and Cancer (Cancer Drug Discovery and Development)

Annotation DNA topoisomerases represent an essential family of DNA processing enzymes and a large number of topoisomerase inhibitors are used clinically for the treatment of various human cancers. Novels drugs are in clinical development both against type I and type II topoisomerases. The book will include basic biochemical and structural reviews for the cancer-relevant topoisomerases. It will describe how topoisomerase dysfunctions can damage the genome and increase the risk of cancers, and the involvement of topoisomerases in programmed cell death. The book will also present the various topoisomerase inhibitors in clinical use and development and their molecular and cellular mechanisms of action Front Matter....Pages i-xi Introduction and Historical Perspective....Pages 1-52 Human DNA Topoisomerase I: Structure, Enzymology and Biology....Pages 53-69 Mitochondrial Topoisomerases....Pages 71-85 Structure and Mechanism of Eukaryotic Type IIA Topoisomerases....Pages 87-101 Essential Functions of Topoisomerase IIIα in the Nucleus and Mitochondria....Pages 103-117 DNA Topoisomerase I and Illegitimate Recombination....Pages 119-143 Topoisomerase-Induced DNA Damage....Pages 145-154 Topoisomerases and Carcinogenesis: Topoisomerase IIIα and BLM....Pages 155-173 Topoisomerases Inhibitors: A Paradigm for Interfacial Inhibition....Pages 175-184 Topoisomerase I Inhibitors: Chemical Biology....Pages 185-210 Topoisomerase II Inhibitors: Chemical Biology....Pages 211-243 Topoisomerase I Inhibitors: Current Use and Prospects....Pages 245-277 Topoisomerase II Inhibitors: Current Use and Prospects....Pages 279-307 Transcriptional Stress by Camptothecin: Mechanisms and Implications for the Drug Antitumor Activity....Pages 309-324 Mechanisms Regulating Cellular Responses to DNA Topoisomerase I-Targeted Agents....Pages 325-334 Tyrosyl-DNA-Phosphodiesterase....Pages 335-354 Ubiquitin and Ubiquitin-Like Proteins in Repair of Topoisomerase-Mediated DNA Damage....Pages 355-379 Repair of Topoisomerase II-Mediated DNA Damage: Fixing DNA Damage Arising from a Protein Covalently Trapped on DNA....Pages 381-407 Topoisomerases and Apoptosis....Pages 409-435 Back Matter....Pages 437-443