Researchers at Utrecht University have engineered a fluorescent sensor that lets scientists observe DNA damage and repair in real time inside living cells and even within whole organisms. Built from components of a natural cellular protein, the tool provides continuous views of repair dynamics while minimizing interference with the cell’s own machinery. The work, reported in Nature Communications, could aid cancer research, drug testing and studies of aging.
DNA inside cells is constantly harmed by sources such as sunlight, chemicals, radiation and normal metabolic activity. Most of this damage is fixed quickly and efficiently, but when repair fails, the resulting errors can contribute to cancer, aging and other diseases, according to Utrecht University researchers.
Until recently, scientists mainly studied these repair events using snapshot methods that required killing and fixing cells at different time points. These approaches offered only isolated views of a highly dynamic process and made it difficult to follow how damage forms and is resolved over time.
The new sensor changes that by enabling real-time monitoring of DNA damage in living systems. It uses a fluorescent tag attached to a small domain derived from one of the cell’s own proteins, which briefly binds to a specific marker that appears on damaged DNA. Because this interaction is gentle and reversible, the sensor can light up sites of damage without substantially disrupting the cell’s repair mechanisms, providing a more realistic picture of the response.
Lead researcher Tuncay Baubec described the advantage in an interview released by Utrecht University: “Our sensor is different. It’s built from parts taken from a natural protein that the cell already uses. It goes on and off the damage site by itself, so what we see is the genuine behavior of the cell.”
Biologist Richard Cardoso da Silva, who engineered and tested the tool, recalled a key moment in the project. “I was testing some drugs and saw the sensor lighting up exactly where commercial antibodies did,” he said. “That was the moment I thought: this is going to work.”
In laboratory experiments, the team used the sensor to follow how damage signals appear and fade over time in cultured cells, capturing the full sequence of DNA repair in a single continuous recording instead of in multiple separate experiments. Researchers could see when damage arose, how quickly repair proteins accumulated at the site and when the signal disappeared as the cell resolved the problem.
The sensor also performed well in a whole organism. Collaborators at Utrecht University tested the protein-based probe in the nematode worm Caenorhabditis elegans, a widely used model in biology. There, it detected programmed DNA breaks that form during development. Baubec said this showed that “the tool is not only for cells in the lab. It can be used as well in real living organisms.”
Because the sensor is modular, scientists can link it to other molecular components. According to Utrecht University’s release, this flexibility could allow researchers to map where DNA damage occurs across the genome, analyze which proteins gather at damaged sites and even move damaged DNA to different positions in the nucleus to test how location influences repair.
Although the sensor is not a treatment, the team expects it to support medical and toxicology research. Many cancer therapies and experimental compounds work by damaging DNA in tumor cells, and early-stage testing often relies on antibodies to gauge how much damage a drug causes. The Utrecht group reports that their live-cell sensor could make such assessments cheaper, faster and more accurate, and may also help in studies of natural aging and in monitoring exposure to radiation or other mutagenic agents.
The work is described in the journal Nature Communications under the title “Engineered chromatin readers track damaged chromatin dynamics in live cells and animals,” led by first author Richard Cardoso da Silva and senior author Tuncay Baubec. Utrecht University says the team has made the tool openly available, with information and constructs shared online so that other laboratories can start using the sensor in their own DNA repair research.
