Related Experiment Video

Updated: Sep 22, 2025

Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications
10:12

Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications

Published on: April 21, 2023

3.0K

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

Christophe Lotz1, Valérie Lamour1,2

  • 1Integrative Structural Biology Department, IGBMC, Université de Strasbourg, CNRS UMR 7104, INSERM U1258, Illkirch 67404, France.

Cancer Drug Resistance (Alhambra, Calif.)
|May 18, 2022
PubMed

Insights

Type 2 topoisomerases (Top2) are crucial for DNA regulation and cancer drug targets. This review explores how post-translational modifications (PTM) affect Top2α in cancer cells and influence drug resistance.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Type 2 DNA topoisomerases (Top2) are essential enzymes regulating DNA topology.
  • Human Topoisomerase II alpha (Top2α) is vital for DNA replication, transcription, and chromosome segregation.
  • Top2α is a key target for anti-cancer drugs and is regulated by post-translational modifications (PTM).

Purpose of the Study:

  • To review the post-translational modifications (PTM) of human Top2α in healthy and cancer cells.
  • To explore the regulation of Top2α by PTM and its role in cancer.
  • To investigate the impact of PTM on resistance to Top2-targeting anti-cancer drugs.

Main Methods:

  • Literature review synthesizing existing research on Top2α structure-function.
  • Analysis of proteomic studies concerning PTM in cancer cells.
  • Overview of Top2α regulation by PTM and its implications for drug resistance.

Main Results:

  • Post-translational modifications (PTM) significantly affect Top2α function and regulation.
  • The extent and impact of PTM on Top2α in cancer cells are not fully characterized.
  • PTM plays a critical role in the development of resistance to Top2-targeting therapies.

Conclusions:

  • Understanding Top2α PTM is crucial for developing effective cancer therapies.
  • Further systematic studies are needed to elucidate the interplay between PTM and Top2 drug resistance.
  • Targeting Top2α PTM may offer novel strategies for overcoming cancer drug resistance.
Keywords:
DNA topoisomerasedrug resistanceetoposidepost-translational modifications

More Related Videos

Simple and Fast Rolling Circle Amplification-Based Detection of Topoisomerase 1 Activity in Crude Biological Samples10:13

Simple and Fast Rolling Circle Amplification-Based Detection of Topoisomerase 1 Activity in Crude Biological Samples

Published on: December 2, 2022

2.8K
Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

10.7K

Related Concept Videos

DNA Topoisomerases02:02

DNA Topoisomerases

Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
32.3K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.4K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.3K
Translesion DNA Polymerases02:10

Translesion DNA Polymerases

Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
10.2K
Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
6.2K
DNA Helicases00:55

DNA Helicases

DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
22.4K