A groundbreaking study conducted by the Kind Group at the Hubrecht Institute has provided new insights into the mechanisms by which cells repair damaged DNA. For the first time, researchers have successfully mapped the activity of DNA repair proteins in individual human cells, revealing how these proteins collaborate within organized “hubs” to fix damage. These findings, published in Nature Communications on November 21, hold significant potential for improving cancer therapies and treatments targeting DNA repair.
DNA, the molecule that carries genetic information, is frequently damaged by internal cellular processes as well as external factors such as ultraviolet radiation and harmful chemicals. Such damage can result in breaks in the DNA strands. When the strands left unrepaired, these breaks can lead to mutations, potentially causing diseases like cancer. To counteract this, cells rely on sophisticated repair systems that employ specialized proteins to locate and fix the damaged regions.
However, the process of DNA repair varies between individual cells, making it crucial to study repair mechanisms at the single-cell level. “Finding breaks in DNA is an enormous challenge,” explained Kim de Luca, the first author of the study. “We often do not know precisely where the damage occurs or why certain regions are more difficult to repair. Our approach has allowed these questions to be answered.”
Mapping DNA Repair Proteins
The researchers utilized advanced techniques to track the activity of repair proteins, mapping where these proteins bind to damaged DNA in individual cells. Unlike previous studies, which relied on an averaged analysis of multiple cells, this approach revealed rare and unique repair processes occurring in specific cells.
“This method allowed us to see how repair proteins interact with damaged regions in individual cells,” De Luca stated. “We found that proteins often organize themselves into hubs, which function like repair cafés, where multiple damaged areas are addressed simultaneously.”
These repair hubs bring together multiple breaks in DNA, enabling repair proteins to work collaboratively in a centralized manner. According to the findings, a single hub can coordinate the repair of up to six different DNA breaks, significantly improving the efficiency of the repair process.
Implications for Medical Treatments
The insights gained from this study have wide-ranging implications, particularly for diseases such as cancer and genetic disorders, where DNA repair plays a critical role. By understanding how cells naturally repair DNA damage, researchers can develop targeted therapies that either enhance or inhibit specific repair mechanisms, depending on the treatment goals.
“Knowledge of DNA repair systems at this level of detail allows the design of treatments that are more effective and less harmful,” De Luca emphasized. The ability to manipulate these repair hubs could lead to the development of novel cancer therapies that exploit the vulnerabilities in tumor cells’ repair mechanisms.
This research highlights the importance of studying DNA repair at the single-cell level and opens new avenues for therapeutic interventions. With further exploration, these findings are expected to have a lasting impact on the treatment of diseases caused by DNA damage.
Reference:
1. de Luca, K.L., Rullens, P.M.J., Karpinska, M.A. et al. Genome-wide profiling of DNA repair proteins in single cells. Nat Commun 15, 9918 (2024). https://doi.org/10.1038/s41467-024-54159-4
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