Advances in DNA damage detection: Current progress, challenges, and future directions

DNA is much continuously exposed to endogenous and exogenous agents that induce damage, potentially leading to genomic instability, disease development, and aging. Detecting DNA damage and understanding associated repair mechanisms are essential for advancing diagnostic techniques, biosensors, and therapeutic interventions. Since DNA damage varies, the desired measurement approach differs, highlighting the need for an unbiased exploration of DNA damage biomarkers, along with a critical analysis of various quantification methods. Therefore, this review aims to provide a comprehensive overview of current methodologies for measuring DNA damage, focusing on direct detection of DNA lesions and indirect measurement of repair enzymes. We discuss various analytical, biochemical, and imaging techniques, identify the limitations in existing technologies and suggest future directions. This review emphasizes the growing need for advanced tools to measure DNA damage, which is set to play a transformative role in early disease detection, optimizing treatments, and supporting safe human space exploration.