Topoisomerase Induced DNA Damage Coupled Diseases and Therapeutic Potential

Abstract

Topoisomerase is an essential enzyme which regulates the topological state of DNA supercoils during replication and transcription. Topoisomerases cleave either one or two DNA strands and then re-join the cleaved strands after passing the intact strand or a double strand through the gap respectively. During relaxation of supercoiled DNA, if topoisomerase is trapped by drugs or alteration of DNA structure, they stabilize topoisomerase-DNA cleavage complex which leads to DNA damage. If Topoisomerase cleavage complex is trapped by any anticancer or others drug, exogenous and endogenous DNA lesion involving mismatches, abasic sites, oxidative damage etc. it may cause DNA damage. DNA damages leads to several diseases such as tumorigenesis, autoimmune disease, Angelman syndrome, SCAN1, SCAR23, Papillary Thyroid Cancer (PTC), cancer therapy-related acute myeloid leukemia. Topoisomerase uses as a potential drug target to manage infectious diseases like leishmaniasis, Chagas disease, pneumococcal, dengue, yellow fever, corona virus, gastrointestinal infection. Here we review the recent information about the topoisomerase mediated DNA damage, related diseases, role of topoisomerase in heterochromatin structure and uses of topoisomerase as drug target in many diseases.

Keywords

• camptothecin
• etoposide
• doxorubicin
• xenotoxic
• non-hodgkin’s lymphoma