DNA can sustain serious injuries called double strand breaks, in which both strands of the helix snap. These breaks are among the most dangerous forms of DNA damage and immediately trigger the cell's damage response. Because DNA damage constantly threatens the stability of our genome, the ability to repair it is vital. When repair systems weaken, diseases can arise. That's why scientists study the molecular pathways of DNA repair: they could lead to new therapies.
But there's a challenge. To truly see how cells fix themselves, scientists need tools that can watch DNA damage in real time. Until recently, this wasn’t possible. Most methods involved stopping and preserving cells at different stages, which only gave snapshots instead of a live view of the repair process.
Now, researchers at Utrecht University have built glowing sensors that show exactly where DNA breaks happen. For the first time, they can watch DNA damage and repair play out live inside cells. It’s like opening a window into the cell’s repair system, revealing the process in real time.
Lead researcher Tuncay Baubec explains how the new innovation offers a novel way to look inside a cell – without interfering with the cell.
"Our sensor is different," says Baubec. "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."
The new tool works in both fixed and live cells, acting like an antibody substitute in standard lab techniques. Using Cas9 to create DNA breaks at chosen sites, researchers showed that the probe can detect single breaks, even in tightly packed heterochromatin, making it a versatile tool for studying DNA repair across different chromatin environments.
The sensor uses a glowing tag linked to a small protein domain from the cell itself. This domain lightly touches a marker on broken DNA, then releases, so the damage is revealed without interfering with repair.
Researchers confirmed that the DNA damage sensor doesn't disrupt natural repair. Because it only briefly binds, it can safely track DNA breaks in living cells and animals. This makes it a powerful tool to watch how DNA damage and repair unfold over time in different systems.
As well as looking at the process in cultured cells the research team tested the sensor in a common worm model organism. It worked just as well there, revealing natural DNA breaks during development. This shows the tool isn't limited to lab-grown cells; it can track DNA damage in real living organisms, too.
The sensor isn't just for watching repair; it can be linked to other molecules. This lets scientists map where DNA breaks happen, see which proteins rush to the site, and even move damaged DNA around inside the nucleus to test what influences repair.
Using an example of how current medicines for cancer are tested, Baubec explains the new tool could completely upend medical research methods.
"Right now, clinical researchers often use antibodies to assess this," Baubec notes. "Our tool could make these tests cheaper, faster, and more accurate."
The study is published in the journal Nature Communications.
Source: Utrecht University
