Related Experiment Video

Updated: May 30, 2026

Simple and Fast Rolling Circle Amplification-Based Detection of Topoisomerase 1 Activity in Crude Biological Samples
10:13

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

Published on: December 2, 2022

Structural basis of type II topoisomerase inhibition by the anticancer drug etoposide

Chyuan-Chuan Wu1, Tsai-Kun Li, Lynn Farh

  • 1Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei City 100, Taiwan.

Science (New York, N.Y.)
|July 23, 2011
PubMed

Insights

Structural insights into human topoisomerase IIβ (TOP2β) reveal how anticancer drugs like etoposide stabilize DNA cleavage complexes. This understanding aids in developing targeted cancer therapies and overcoming drug resistance.

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Pharmacology

Background:

  • Type II topoisomerases (TOP2s) are crucial enzymes that manage DNA topology by transiently cleaving both DNA strands.
  • Many anticancer drugs function by stabilizing TOP2 cleavage complexes, leading to DNA breaks and cancer cell death.

Purpose of the Study:

  • To elucidate the structural basis of etoposide-induced stabilization of human TOP2β cleavage complexes.
  • To understand the structure-activity relationships of etoposide derivatives and drug resistance mechanisms.

Main Methods:

  • Determined the crystal structure of a large fragment of human TOP2β.
  • Co-crystallized the TOP2β fragment with DNA and the anticancer drug etoposide.

Main Results:

  • Revealed detailed structural interactions between TOP2β, DNA, and etoposide.
  • Explained how etoposide stabilizes the TOP2 cleavage complex at a molecular level.
  • Provided insights into etoposide derivative activity and drug-resistant mutations.

Conclusions:

  • The study provides a structural foundation for understanding etoposide's mechanism of action.
  • Findings can inform the design of novel, isoform-specific TOP2-targeting anticancer drugs.
  • Understanding drug-target interactions is key to overcoming therapeutic resistance.

More Related Videos

Quantitative Detection of DNA-Protein Crosslinks and Their Post-Translational Modifications10:12

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

Published on: April 21, 2023

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

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.  Type I...
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
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...
Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...