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Soren et al. Cancer Drug Resist 2020;3:18-25 Cancer
DOI: 10.20517/cdr.2019.106 Drug Resistance

Review Open Access

Topoisomerase IB: a relaxing enzyme for stressed
DNA

Bini Chhetri Soren , Jagadish Babu Dasari , Alessio Ottaviani , Federico Iacovelli , Paola Fiorani 1,2
1,#
1
2
1
1 Department of Biology, University of Rome Tor Vergata, Rome 00133, Italy.
2 Institute of Translational Pharmacology, National Research Council, Rome 00133, Italy.
# Present address: Department of Research and Application Development, Biogenex Life Sciences, Telangana 501510, India.
Correspondence to: Dr. Paola Fiorani, Institute of Translational Pharmacology, National Research Council, CNR, Via Del
Fosso del Cavaliere 100, Rome 00133, Italy. E-mail: paola.fiorani@uniroma2.it
How to cite this article: Soren BC, Dasari JB, Ottaviani A, Iacovelli F, Fiorani P. Topoisomerase IB: a relaxing enzyme for
stressed DNA. Cancer Drug Resist 2020;3:18-25. http://dx.doi.org/10.20517/cdr.2019.106

Received: 5 Nov 2019 First Decision: 3 Dec 2019 Revised: 10 Dec 2019 Accepted: 18 Dec 2019 Published: 19 Mar 2020

Science Editor: Robert C. A. M. van Waardenburg Copy Editor: Cai-Hong Wang Production Editor: Tian Zhang

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-D NA 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.

Keywords: Human DNA topoisomerase IB, mechanism of action, drugs inhibition

DNA TOPOISOMERASE I
Topoisomerase I (TopI) is a class of enzymes responsible for catalyzing the relaxation of supercoiled DNA
during cell essential processes such as DNA replication, transcription, recombination, and chromosome
[1,2]
condensation . TopI enzymes are not dependent on ATP for their catalytic activity, except for reverse
© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
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