Related Experiment Video
Updated: Feb 24, 2026
Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
Role of Protein Linked DNA Breaks in Cancer
Walaa R Allam1, Mohamed E Ashour2, Amr A Waly2
1Center for Genomics, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza, Egypt. wallam@zewailcity.edu.eg.
Abstract:
Topoisomerases are a group of specialized enzymes that function to maintain DNA topology by introducing transient DNA breaks during transcription and replication. As a result of abortive topoisomerases activity, topoisomerases catalytic intermediates may be trapped on the DNA forming topoisomerase cleavage complexes (Topcc). Topoisomerases trapping on the DNA is the mode of action of several anticancer drugs, it lead to formation of protein linked DAN breaks (PDBs). PDBs are now considered as one of the most dangerous forms of endogenous DNA damage and a major threat to genomic stability. The repair of PDBs involves both the sensing and repair pathways. Unsuccessful repair of PDBs leads to different signs of genomic instabilities such as chromosomal rearrangements and cancer predisposition. In this chapter we will summarize the role of topoisomerases induced PDBs, identification and signaling, repair, role in transcription. We will also discuss the role of PDBs in cancer with a special focus on prostate cancer.
Insights
Topoisomerase trapping on DNA forms dangerous protein-linked DNA breaks (PDBs), a major threat to genomic stability. Understanding PDB repair is crucial for preventing cancer and genomic instability.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Topoisomerases regulate DNA topology by creating transient breaks.
- Abortive topoisomerase activity can lead to trapped catalytic intermediates, forming protein-linked DNA breaks (PDBs).
- PDBs are a significant source of endogenous DNA damage and a threat to genomic stability.
Purpose of the Study:
- To summarize the role of topoisomerase-induced PDBs.
- To discuss PDB identification, signaling, and repair pathways.
- To explore the involvement of PDBs in transcription and cancer, particularly prostate cancer.
Main Methods:
- Review of existing literature on topoisomerases and DNA damage.
- Analysis of mechanisms for PDB formation and repair.
- Discussion of the link between PDBs and genomic instability in cancer.
Main Results:
- Topoisomerase trapping is a mechanism for anticancer drugs, inducing PDBs.
- PDBs are critical endogenous DNA lesions impacting genomic stability.
- Failed PDB repair contributes to chromosomal rearrangements and cancer predisposition.
Conclusions:
- Topoisomerase-induced PDBs are a key factor in DNA damage and genomic instability.
- Effective PDB repair pathways are essential for maintaining genome integrity.
- Further research into PDBs, especially in prostate cancer, is warranted.
More Related Videos
08:31Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy
Published on: June 8, 2018
06:44Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging
Published on: April 28, 2021
Related Concept Videos
02:04Fixing Double-strand Breaks
02:04Fixing Double-strand Breaks
01:38Nucleotide Excision Repair
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
01:08Nucleotide Excision Repair
02:36DNA Damage Can Stall the Cell Cycle
02:36DNA Damage can Stall the Cell Cycle