New Sensor Enables Real-Time Observation of DNA Repair

Utrecht University researchers have unveiled a new fluorescent sensor that enables real-time observation of DNA repair processes within living cells, offering promising advancements in cancer research, drug development and understanding aging.

Researchers at Utrecht University in the Netherlands have developed an innovative fluorescent sensor that allows scientists to observe DNA repair processes in real time within living cells. This groundbreaking technology, published in the journal Nature Communications, holds the potential to significantly advance cancer research, drug safety testing and studies of aging.

Ordinarily, DNA within cells is constantly damaged by various factors such as sunlight, chemicals and radiation. Cells usually repair this damage efficiently, but failures in these repair mechanisms can lead to aging, cancer and other diseases.

Until now, researchers have struggled to observe these repair processes in living cells, often relying on methods that involved killing and fixing cells, providing only static snapshots.

The new sensor from Utrecht University marks a significant shift. It enables continuous observation of DNA damage and repair in both living cells and organisms.

“Our sensor is different,” lead researcher Tuncay Baubec, a professor and chair of genome biology & epigenetics at Utrecht University, said in a news release. “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.”

The sensor operates by attaching a fluorescent tag to a domain derived from a protein used by the cell, which briefly binds to a marker on damaged DNA. This interaction is both gentle and reversible, illuminating the damage without hindering the cell’s repair process.

Richard Cardoso Da Silva, the biologist who engineered and tested the tool, highlighted a breakthrough moment.

“I was testing some drugs and saw the sensor lighting up exactly where commercial antibodies did,” he said in the news release. “That was the moment I thought: this is going to work.”

The implications of this advancement are profound.

Previously, researchers needed to conduct numerous separate experiments to capture different time points of DNA repair.

Now, they can observe the entire repair process in a single continuous sequence, providing a higher resolution and a more realistic picture of cellular behavior.

The research team didn’t stop at cell cultures.

Collaborators at Utrecht University tested the sensor in C. elegans, a commonly used model organism. The sensor effectively revealed programmed DNA breaks during the worm’s development, demonstrating the tool’s applicability beyond lab cell cultures.

“It showed that the tool is not only for cells in the lab. It can be used as well in real living organisms,” added Baubec.

Looking forward, this sensor opens up numerous avenues for further research. It can be attached to other molecular components enabling the mapping of DNA damage across the genome and identifying the proteins that congregate around damaged sites.

“Depending on your creativity and your question, you can use this tool in many ways,” Cardoso Da Silva added.

While the sensor is not a direct medical treatment, it has the potential to revolutionize medical research. It could make DNA damage assessment cheaper, faster and more accurate in early drug development and cancer therapy research.

“Right now, clinical researchers often use antibodies to assess this,” added Baubec. “Our tool could make these tests cheaper, faster and more accurate.”

The Utrecht University team has made this pioneering tool available to the broader scientific community, encouraging researchers to utilize the sensor in their own studies.

“All information is available online. Scientists can use it immediately,” Baubec added.

Source: Utrecht University