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Updated: Jun 23, 2026

Assessment of DNA Double Strand Break Repair Activity Using High-throughput and Quantitative Luminescence-Based Reporter Assays
Published on: June 14, 2024
The DNA-damage response: new molecular insights and new approaches to cancer therapy
1Department of Zoology, The Gurdon Institute, University of Cambridge, Cambridge, UK. s.jackson@gurdon.cam.ac.uk
Abstract:
The DNA of all cells is continually under assault from a wide range of DNA-damaging agents. To counter this threat to their genetic integrity, cells possess systems, collectively known as the DDR (DNA-damage response), to detect DNA damage, signal its presence and mediate its repair. In the present article, I provide an overview of the DDR and then describe how work in my laboratory and elsewhere has identified some of the key protein players that mediate cellular responses to the most cytotoxic form of DNA damage: the DNA DSB (double-strand break). I also discuss some of my laboratory's recent work, which has revealed that the way cells respond to DSBs is modulated in a cell-cycle-dependent manner to ensure that the cell uses the DSB repair system that is most suited to its cell-cycle stage. Finally, I explain how our increasing knowledge of the DDR is suggesting new avenues for treating cancer and provide an example of a DDR-inhibitory drug that is showing promise in clinical trials.
Insights
Cells have a DNA-damage response (DDR) to repair DNA double-strand breaks (DSBs). This response is cell-cycle dependent, and understanding it offers new cancer treatment strategies.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- DNA is constantly exposed to damaging agents, threatening genetic integrity.
- The DNA-damage response (DDR) is a critical cellular system for detecting and repairing DNA damage.
- DNA double-strand breaks (DSBs) represent a particularly cytotoxic form of DNA damage.
Discussion:
- Key protein players mediating cellular responses to DSBs have been identified.
- The cellular response to DSBs is modulated by the cell cycle.
- This cell-cycle dependency ensures the appropriate DSB repair system is utilized based on the cell's stage.
Key Insights:
- Identification of crucial proteins involved in the DNA-damage response.
- Discovery of cell-cycle-dependent regulation of DNA double-strand break repair pathways.
- Understanding how cells prioritize specific repair mechanisms according to their cell-cycle stage.
Outlook:
- Advances in understanding the DDR are paving the way for novel cancer therapies.
- DDR-inhibitory drugs are emerging as promising therapeutic agents in clinical trials.
- Targeting the DDR offers a potential strategy to enhance cancer treatment efficacy.
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