Ultraviolet (UV) radiation from the sun is a well-known cause of DNA damage, which can lead to diseases like skin cancer. But how do our cells repair this damage to protect us? Researchers from Sabanci University, Veysel Oğulcan Kaya and Ogün Adebali, have uncovered a fascinating answer: when DNA is damaged by UV light, our cells reorganize their genetic material in 3D space to prioritize repair, in what might be called a "cellular rescue mission."
A New Look at DNA Repair
DNA, the blueprint of life, is not just a long string of genetic instructions—it's carefully folded and packed within our cells. This folding isn't random; it's part of a complex system that allows the cell to access specific parts of the DNA when needed, such as during repair processes.
When UV radiation strikes, it creates lesions—tiny injuries—that can block essential cellular functions. But these injuries don't happen in isolation. The entire structure of the cell's DNA adjusts, helping specialized repair teams reach the damaged spots more effectively.
"DNA isn't just a static code. It's dynamic and incredibly responsive," said Ogün Adebali, the principal investigator overseeing the research. "The way DNA is organized helps the cell act quickly to repair damage."
Rearranging DNA for Repair
Imagine your genome as a library, where books (genes) are stored on shelves (sections of DNA). When UV damage occurs, the library's shelves rearrange themselves, bringing damaged books closer to repair tools. This movement makes the repair process faster and more efficient.
To uncover these patterns of DNA reorganization, the researchers used a cutting-edge deep learning framework. By analyzing vast amounts of genomic data, this approach helped them detect subtle changes in how DNA regions interact with one another after UV damage. This advanced method revealed not only where the damage occurs but also how the genome reshapes itself to prioritize repairs.
The researchers found that areas of the genome—where the DNA is especially active and accessible—are prioritized for repair. These regions are like high-traffic zones in the library, ensuring that the most critical books are fixed first. This helps cells maintain essential functions, even under stressful conditions like UV exposure.
DNA Damage Response: More Than Just Repair
In addition to fixing damaged DNA, the researchers discovered that UV radiation triggers changes in gene activity. Some genes, particularly those involved in coordinating the cell's defense, become more active. These genes produce proteins that help the cell survive and recover.
For example, genes like JUN and FOS, which are part of the cell's emergency response system, are quickly turned on after UV exposure. These genes help control inflammation and protect cells from dying.
"What's remarkable is witnessing this intricate coordination between the 3D genome, transcription and DNA repair," said Veysel Oğulcan Kaya, the primary author of the study. "What surprised us most was how quickly the DNA damage response happens—within just 12 minutes after UV exposure. Even more surprising is that we could observe early signs of recovery within the first 30 minutes."
Why It Matters
This research provides new insights into how cells maintain their genetic integrity. By mapping how DNA moves and how certain genes are activated during repair, the study offers clues about why some people might be more resistant to UV-related diseases than others.
The team hopes these findings will inspire new strategies for preventing and treating conditions like skin cancer. Understanding the "rules" behind DNA's reorganization could help scientists design better drugs or therapies to boost the body's natural repair processes.
What's Next?
The researchers are already planning to study how other environmental hazards, such as pollutants or carcinogens, affect DNA's organization and repair mechanisms. They also aim to refine their methods to gain even clearer insights into how DNA repair works.
"This study is just the beginning," Adebali said. "Our findings open the door to exploring how cells protect themselves from a wide range of stresses, not just UV damage."
Supported by funding from TÜBITAK, this research highlights the remarkable adaptability of our cells in safeguarding the very blueprint of life. It's a story of resilience, precision, and the incredible machinery that keeps us alive, even in the face of everyday challenges like sunlight.
The study was published in Nature Communications on February 5, 2025, offering a detailed look at the dynamic response of DNA to UV-induced damage and its repair mechanisms.
