Fluorescent Sensor Enables Real-Time Observation of DNA Damage and Repair

A new fluorescent sensor developed at Utrecht University allows scientists to watch DNA damage and repair in real time within living cells, something not possible with other methods. DNA in cells faces constant threats from sunlight, chemicals, and everyday cellular processes, and while most damage is repaired efficiently, failures in repair can contribute to diseases such as cancer and also accelerate aging.

Historically, observing DNA repair as it happens was challenging because standard techniques required killing and fixing cells at different time points, providing only static snapshots. The Utrecht team has now changed this paradigm. Their sensor is built from a part of a natural protein used by cells and is designed to attach a fluorescent tag that binds gently and reversibly to a marker on damaged DNA. This approach avoids interfering with the cell’s own repair machinery, allowing researchers to observe natural repair processes without disruption. “Our sensor is different,” explains Tuncay Baubec, senior author on the study published in Nature Communications. “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 behaviour of the cell.”

First author Richard Cardoso Da Silva engineered and tested the sensor and remembers clearly when he realized they had something special. “I was testing some drugs and saw the sensor lighting up exactly where commercial antibodies did,” he says. “That was the moment I thought: this is going to work.”

This sensor has also been successfully tested in living organisms, such as C. elegans, where it illuminated DNA breaks during development. Its modularity means it can be used to map damage locations, track proteins involved in repair, or manipulate DNA within the nucleus to investigate repair factors. Baubec points out that the sensor, while not a treatment, could make research into cancer therapies and drug testing cheaper, faster, and more accurate, and it may also be useful for studying natural ageing and environmental exposures.

The team has made the tool freely available to the research community, supporting broader adoption and collaboration.