Dr. Choi Jun-Hyuk still remembers the moment in 2015 when his team at the Korea Research Institute of Standards and Science first caught a glimpse of something remarkable: trace DNA repair fragments floating within living cells, almost too faint to detect. It was a glimpse that would eventually lead to a breakthrough now published in the journal Nucleic Acids Research — a technology sensitive enough to detect DNA damage at the molecular level, with precision 22 times greater than conventional methods.
The platform, a competitive immunoassay developed over more than a decade of painstaking work by KRISS's Biometrology Group and Organic Metrology Group, can quantify damaged DNA fragments down to the level of just several thousand molecules. This matters enormously because inside every human cell, DNA is under constant assault — from ultraviolet light, chemical agents, cigarette smoke, even the normal metabolic processes of life itself. When damage goes unrepaired, mutations accumulate, potentially leading to aging and diseases like cancer.
To protect genomic integrity, cells deploy the Nucleotide Excision Repair system, which snips out damaged DNA segments and replaces them with fresh genetic material. The tiny fragments discarded in this process are called Small Excised Damaged DNA, or sedDNA, and their abundance reveals how efficiently a cell's repair machinery is working.
The challenge has always been measuring those fragments accurately. Traditional methods label the ends of excised DNA molecules and estimate quantity based on signal strength — but there's a catch. Enzymatic degradation can chew up those ends inside the cell, preventing proper labeling and causing researchers to systematically undercount what actually exists.
KRISS's approach sidesteps this problem entirely. Rather than targeting fragment ends, the team immobilizes synthetic DNA that mimics damaged structures onto a microplate as a reference. Cellular DNA extracts are then mixed with antibodies specifically designed to recognize damaged structures. The antibodies compete for binding between sample fragments and the reference material on the plate, allowing researchers to calculate fragment abundance with far greater accuracy, converting the results into molar concentrations and ultimately into precise fragment counts.
The implications stretch from the laboratory into the clinic. According to Dr. Choi, quantifying DNA repair efficiency could enable early assessment of cancer risk and provide an objective measure of how individual cells respond to anticancer drugs. The team plans further validation using human tissue samples, which could eventually bring this technology into personalized treatment planning.
"This approach enables researchers to directly quantify the number of DNA repair fragments generated in cells, providing a robust basis for precision analysis of DNA repair dynamics and cellular responses," the researchers noted. The KRISS team collaborated with a researcher from Wright State University in the United States on the project, published in Nucleic Acids Research.
For millions of people worldwide, this kind of early warning system represents something precious: a window of time, and a chance to act before damage becomes disease.