Related Experiment Video
Updated: Apr 2, 2026

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
Therapeutic opportunities within the DNA damage response
Laurence H Pearl1, Amanda C Schierz2, Simon E Ward3
1Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK.
Abstract:
The DNA damage response (DDR) is essential for maintaining the genomic integrity of the cell, and its disruption is one of the hallmarks of cancer. Classically, defects in the DDR have been exploited therapeutically in the treatment of cancer with radiation therapies or genotoxic chemotherapies. More recently, protein components of the DDR systems have been identified as promising avenues for targeted cancer therapeutics. Here, we present an in-depth analysis of the function, role in cancer and therapeutic potential of 450 expert-curated human DDR genes. We discuss the DDR drugs that have been approved by the US Food and Drug Administration (FDA) or that are under clinical investigation. We examine large-scale genomic and expression data for 15 cancers to identify deregulated components of the DDR, and we apply systematic computational analysis to identify DDR proteins that are amenable to modulation by small molecules, highlighting potential novel therapeutic targets.
Insights
The DNA damage response (DDR) is crucial for genomic stability and cancer development. This study analyzes 450 DDR genes, identifying potential new therapeutic targets for cancer treatment.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- The DNA damage response (DDR) is vital for maintaining genomic integrity.
- Disruptions in DDR pathways are a hallmark of cancer.
- Targeting DDR components offers a promising strategy for cancer therapy.
Purpose of the Study:
- To provide an in-depth analysis of 450 curated human DDR genes.
- To explore the function, role in cancer, and therapeutic potential of DDR genes.
- To identify novel therapeutic targets within the DDR pathway.
Main Methods:
- Expert curation of 450 human DDR genes.
- Analysis of large-scale genomic and expression data across 15 cancer types.
- Systematic computational analysis to identify druggable DDR proteins.
Main Results:
- Comprehensive overview of DDR gene function and cancer relevance.
- Identification of deregulated DDR components in various cancers.
- Highlighting of DDR proteins as potential targets for small molecule therapeutics.
Conclusions:
- DDR proteins represent a rich source of potential cancer drug targets.
- Understanding DDR pathway dysregulation is key to developing novel cancer therapies.
- Computational approaches can effectively identify druggable targets within complex biological pathways.
More Related Videos
Related Concept Videos
DNA Damage can Stall the Cell Cycle
DNA Damage Can Stall the Cell Cycle
Overview of DNA Repair
Chemically...
Overview of DNA Repair
Nucleotide 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...
Nucleotide Excision Repair

