Topoisomerases are ubiquitous enzymes that control the topological state of the DNA genome by concerted breaking and rejoining the DNA strands. Type I topoisomerases break and rejoin a single DNA strand at a time during catalysis while type II topoisomerases break and rejoin a double strand of DNA. Topoisomerases are targeted by antibacterial and anticancer drugs used in the clinic. The drug discovery efforts require the basic understanding of the structure, mechanism and functions of topoisomerases. Type IA topoisomerases in bacteria and type IB topoisomerases in human play important roles in relief of transcription driven supercoiling of DNA. This function of topoisomerases during transcription is especially important during stress response. Antibiotic resistance is a serious global health problem that requires exploration of new targets for discovery of novel antibiotics. The type IA topoisomerase I present in many bacterial pathogens, including <i>Mycobacterium tuberculosis</i>, is being targeted by interdisciplinary collaborations combining approaches of high throughput screening, structural biology, computational docking and medicinal chemistry. Novel inhibitors of human type IB topoisomerase may provide new treatment for cancer as well as other diseases.

Functional roles of topoisomerases in transcription: Relevance for basis and treatment of human diseases

2019 Spring National Meeting

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