Researchers at the Spanish National Cancer Research Centre (CNIO) have introduced the 'human reparome' in early October 2025, a comprehensive atlas detailing how approximately 20,000 human genes affect the repair of DNA double-strand breaks. Published in the journal Science, this catalog offers significant insights into genome stability mechanisms and is expected to revolutionize personalized cancer treatments and gene editing technologies.
The creation of the human reparome involved an extensive process where scientists systematically inactivated each human gene in separate cell populations, resulting in nearly 20,000 distinct cell lines. These modified cells were then induced to experience DNA double-strand breaks using CRISPR-Cas9 gene editing technology. The subsequent repair processes left unique molecular signatures, known as 'mutational footprints,' on the DNA. These signatures were cataloged using high-throughput sequencing and advanced computational analysis, allowing researchers to understand how the absence or malfunction of specific genes impacts DNA repair pathways—a critical element of cellular health and disease.
The implications of this research are profound, particularly for oncology. Many cancer treatments, including chemotherapy and radiotherapy, work by intentionally damaging DNA to eliminate cancer cells. However, tumors can develop resistance by enhancing their DNA repair capabilities. The human reparome serves as a powerful tool to identify these altered repair mechanisms within tumors, paving the way for precision oncology strategies that can specifically target and disrupt tumor DNA repair pathways, thereby overcoming resistance and improving patient outcomes.
Understanding these repair mechanisms is also vital for advancing gene editing technologies like CRISPR-Cas9, aiming for greater precision and minimizing unintended genetic consequences. The REPAIRome portal is now publicly accessible, encouraging global researchers to investigate the complex relationships between genes and DNA repair. This collaborative resource is anticipated to accelerate discoveries in cancer biology, genomics, and biotechnology, leading to novel therapeutic interventions and a deeper comprehension of genome integrity. The development of the human reparome marks a significant advancement in functional genomics, demonstrating the power of integrated research in tackling complex biological challenges and offering new hope for more effective cancer treatments and safer gene editing applications. The project was supported by various Spanish and European public bodies, including the Ministry of Science, Innovation and Universities, the Spanish Research Agency (AEI), the European Regional Development Fund, as well as prominent private foundations.