Topoisomerase IB: a relaxing enzyme for stressed DNA.

Content Provider	Europe PMC
Author	Soren, Bini Chhetri Dasari, Jagadish Babu Ottaviani, Alessio Iacovelli, Federico Fiorani, Paola
Abstract	DNA topoisomerase I enzymes relieve the torsional strain in DNA; they are essential for fundamental molecular processes such as DNA replication, transcription, recombination, and chromosome condensation; and act by cleaving and then religating DNA strands. Over the past few decades, scientists have focused on the DNA topoisomerases biological functions and established a unique role of Type I DNA topoisomerases in regulating gene expression and DNA chromosome condensation. Moreover, the human enzyme is being investigated as a target for cancer chemotherapy. The active site tyrosine is responsible for initiating two transesterification reactions to cleave and then religate the DNA backbone, allowing the release of superhelical tension. The different steps of the catalytic mechanism are affected by various inhibitors; some of them prevent the interaction between the enzyme and the DNA while others act as poisons, leading to TopI-DNA lesions, breakage of DNA, and eventually cellular death. In this review, our goal is to provide an overview of mechanism of human topoisomerase IB action together with the different types of inhibitors and their effect on the enzyme functionality.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC9094055&blobtype=pdf
Journal	Cancer Drug Resistance [Cancer Drug Resist]
Volume Number	3
DOI	10.20517/cdr.2019.106
PubMed Central reference number	PMC9094055
Issue Number	1
PubMed reference number	35582040
e-ISSN	2578532X
Language	English
Publisher	OAE Publishing Inc.
Publisher Date	2020-03-19
Access Restriction	Open
Rights License	© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. © The Author(s) 2020.
Subject Keyword	Human DNA topoisomerase IB mechanism of action drugs inhibition
Content Type	Text
Resource Type	Article
Subject	Pharmacology (medical) Cancer Research