Benu Brata Das
Indian Association for the Cultivation of Science, India
Title: DNA topoisomerase -I in life and death: New chemotherapeutic opportunities are on the horizon
Biography
Biography: Benu Brata Das
Abstract
Topoisomerase I (Top1) regulates DNA supercoiling and is essential for all DNA transactions including replication, transcription and recombination. Top1 is the target of anticancer drug [camptotecin (CPT)] and its clinical derivatives (irinotecan and topotecan), as it forms Top1 cleavage complexes (Top1cc) that are trapped by the drugs leading to stable enzyme-DNA covalent complexes. The normally transient Top1-induced DNA single-strand breaks evolve into double-strand breaks, which are detrimental to the cell and ultimately lead to cell death. Hence, the repair of Top1cc is an important part of DNA metabolism and cancer resistance. Tyrosyl-DNA phosphodiesterase 1 (TDP1), a key repair enzyme for trapped Top1cc, hydrolyzes the phosphodiester bond between the DNA 3\'-end and the Top1-tyrosyl moiety. Here, we will discuss how targeting DNA repair pathways could potentially synergize Top1 inhibitors in cancer chemotherapy.