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Lotz et al. Cancer Drug Resist 2020;3:149-60 Cancer
DOI: 10.20517/cdr.2019.114 Drug Resistance

Review Open Access

The interplay between DNA topoisomerase 2a post-
translational modifications and drug resistance

Christophe Lotz , Valérie Lamour 1,2
1
1 Integrative Structural Biology Department, IGBMC, Université de Strasbourg, CNRS UMR 7104, INSERM U1258, Illkirch 67404,
France.
2 Hôpitaux Universitaires de Strasbourg, Strasbourg 67000 France.

Correspondence to: Dr. Valérie Lamour, Integrative Structural Biology Department, IGBMC, 1 rue Laurent Fries, Illkirch Cedex
67404, France. E-mail: lamourv@igbmc.fr
How to cite this article: Lotz C, Lamour V. The interplay between DNA topoisomerase 2a post-translational modifications and
drug resistance. Cancer Drug Resist 2020;3:149-60. http://dx.doi.org/10.20517/cdr.2019.114
Received: 17 Dec 2019 First Decision: 13 Jan 2020 Revised: 19 Jan 2020 Accepted: 5 Feb 2020 Available online: 27 Feb 2020

Science Editor: Robert C.A.M. van Waardenburg Copy Editor: Jing-Wen Zhang Production Editor: Jing Yu

Abstract

The type 2 DNA topoisomerases (Top2) are conserved enzymes and biomarkers for cell proliferation. The catalytic
activities of the human isoform Top2a are essential for the regulation of DNA topology during DNA replication,
transcription, and chromosome segregation. Top2a is a prominent target for anti-cancer drugs and is highly
regulated by post-translational modifications (PTM). Despite an increasing number of proteomic studies, the extent
of PTM in cancer cells and its importance in drug response remains largely uncharacterized. In this review, we
highlight the different modifications affecting the human Top2a in healthy and cancer cells, taking advantage of
the structure-function information accumulated in the past decades. We also overview the regulation of Top2a by
PTM, the level of PTM in cancer cells, and the resistance to therapeutic compounds targeting the Top2 enzyme.
Altogether, this review underlines the importance of future studies addressing more systematically the interplay
between PTM and Top2 drug resistance.

Keywords: DNA topoisomerase, drug resistance, post-translational modifications, etoposide

INTRODUCTION
The type 2 DNA topoisomerases (Top2) are evolutionary conserved enzymes and biomarkers for
[1]
cell proliferation . They are involved in essential cellular processes such as DNA replication, DNA
[2]
transcription, and chromosome segregation . The human Top2a isoform is highly expressed during
© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
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