The advancement, which has facilitated previously unattainable experiments, is detailed in the journal Nature Communications.
The DNA within cells is perpetually subject to harm from factors like solar radiation, chemical substances, radioactivity, or inherent biological functions. Typically, cells rectify this impairment swiftly and effectively. However, unsuccessful repair can lead to severe repercussions, playing a role in aging, cancer development, and various other ailments.
Previously, observing these repair mechanisms in real-time presented considerable challenges for scientists. The majority of methodologies required the termination and stabilization of cells at various intervals, yielding only static representations of the activity.
DNA Damage Sensor
This novel instrument revolutionizes the study of DNA damage. This DNA damage sensor enables scientists to monitor the formation and disappearance of damage in living cells and organisms.
Lead researcher Tuncay Baubec describes the innovation as a means to look into the cell “without disrupting the cell”. Existing tools, like antibodies or nanobodies, often bind too tightly to DNA, potentially disrupting the cell's repair mechanisms.
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.
Tuncay Baubec, Lead Researcher, Utrecht University
“This is Going to Work”
The sensor functions by linking a fluorescent tag to a small domain derived from a cellular protein. This domain briefly binds to a marker on damaged DNA, illuminating the damage without impeding the repair process due to its gentle and reversible interaction.
Biologist Richard Cardoso da Silva recalls the moment of realizing the tool's significance during its engineering and testing. “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.”
The advancement from previous methodologies is substantial.
Rather than tediously conducting ten individual experiments to document ten distinct time intervals, researchers now possess the capability to monitor the complete repair mechanism in a singular, uninterrupted visual recording. This enables observation of the onset of damage, the rate at which repair proteins accumulate, and the point at which the cell effectively rectifies the issue.
You get more data, higher resolution and, importantly, a more realistic picture of what actually happens inside a living cell.
Richard Cardoso da Silva, Biodynamics and Biocomplexity, Utrecht University
From Cells in the Lab to Living Organisms
The research group's efforts extended beyond merely cultured cells. Associates at Utrecht University assessed the protein's efficacy within the nematode C. elegans, a prevalent model organism in biological studies.
The sensor exhibited comparable performance in this context, exposing programmed DNA breaks that arise during the worm's developmental stages. According to Baubec, this represented a pivotal juncture. “It showed that the tool is not only for cells in the lab. It can be used as well in real living organisms.”
Discovering What Affects Repair
The potential applications now extend significantly beyond mere observation of repair processes. The protein can be readily conjugated to other molecular components.
Consequently, researchers can employ it to delineate the genomic locations of DNA damage and ascertain the proteins that congregate around a compromised site. Furthermore, they can relocate damaged DNA to alternative positions within the cell nucleus to ascertain the variables influencing repair.
“Depending on your creativity and your question, you can use this tool in many ways,” says Cardoso da Silva.
More Accurate Medical Research
While the sensor is not a form of medical intervention, it has the potential to impact medical investigations. A number of cancer treatments, for instance, function by purposefully inflicting harm to the DNA of cancerous cells. During the initial phases of pharmaceutical creation, it is essential for researchers to precisely evaluate the degree of DNA impairment induced by a substance.
Right now, clinical researchers often use antibodies to assess this. Our tool could make these tests cheaper, faster, and more accurate.
Tuncay Baubec, Lead Researcher, Utrecht University
The investigators also foresee applications in medical settings, spanning from the examination of inherent aging mechanisms to the identification of radiation or mutagenic contact.
Available for all Researchers
This instrument has garnered substantial interest. Prior to its publications, other research facilities reached out, keen to incorporate the sensor into their individual studies on DNA repair. To facilitate this, the team has ensured the tool is accessible to all. “All information is available online. Scientists can use it immediately,” Baubec says.
Reader eGFP
This footage shows the fluorescent sensors in action inside a living cell. They appear as bright green spots the moment they bind to sites of DNA damage. Video Credit: Utrecht University
Journal Reference:
da Silva, R. C., et al. (2025). Engineered chromatin readers track damaged chromatin dynamics in live cells and animals. Nature Communications. DOI:10.1038/s41467-025-65706-y.