Related Experiment Video
Updated: Aug 14, 2026

Atomic Force Microscopy Investigations of DNA Lesion Recognition in Nucleotide Excision Repair
Published on: May 24, 2017
Topoisomerase II-mediated DNA cleavage by amonafide and its structural analogs
Y H Hsiang1, J B Jiang, L F Liu
1Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Abstract:
Treatment of SV40-infected monkey cells with amonafide (benzisoquinolinedione), an intercalative antitumor drug, resulted in rapid accumulation of linearized intracellular SV40 DNA molecules that were protein linked. Studies using purified mammalian DNA topoisomerase II have shown that amonafide and its structural analogs interfere with the breakage-rejoining reaction of the enzyme by stabilizing a reversible enzyme-DNA "cleavable complex." Denaturation of the cleavable complex with sodium dodecyl sulfate resulted in DNA cleavage and the covalent association of topoisomerase II polypeptides with the cleaved DNA. Unwinding measurements indicate that amonafide is a DNA intercalator. These results suggest that amonafide and its structural analogs (e.g., mitonafide) represent a new class of intercalative topoisomerase II-active antitumor drugs. Different from other topoisomerase II-active antitumor drugs, amonafide and mitonafide induce specific DNA cleavage at a single major site on pBR322 DNA. The strong site specificity of amonafide may allow detailed characterization of the intercalator-stabilized, topoisomerase II-DNA cleavable complex.
Related Concept Videos
DNA Topoisomerases
Types and Mechanism of action
Topoisomerases are divided into two main types. Type I...
Restarting Stalled Replication Forks
Conservative Site-specific Recombination and Phase Variation
The recognition sites for Cre recombinase called LoxP...
Restriction Enzymes
The host bacteria protect their own genomic DNA from these enzymes by methylating these sites. Some...
Maxam-Gilbert Sequencing
Challenges of the Maxam-Gilbert Method
The...
Inhibitors of Bacterial DNA Synthesis

