Ultraviolet (UV) radiation is known to cause DNA damage, and while that damage may accumulate and eventually lead to diseases like skin cancer, cells also have repair mechanisms that can fix UV-induced DNA damage. Scientists have now learned more about how the genome can be physically rearranged to ensure that repairing DNA damage is the cell's priority. The work was published in the journal Nature Communications.
DNA has to be carefully folded. It's a huge molecule that must be properly packaged so that it not only fits into the tiny nucleus of each cell, but also makes the right genes available for activity. But UV radiation may cause small rips or lesions in DNA that can interfere with cellular functions. But the structure of DNA will adjust so that those lesions are effectively identified and repaired.
"DNA isn't just a static code. It's dynamic and incredibly responsive," said corresponding study author Ogün Adebali. "The way DNA is organized helps the cell act quickly to repair damage."
In this study, the researchers analyzed genomic data and found subtle changes in the interactions between different parts of DNA after UV damage had occurred. The investigators found where DNA damage happened, then how the genome reorganized itself so that repairs were conducted. The places where the genome was most active were also most highly prioritized for repair. As such, the most critical cellular functions are still carried out even after UV damage.
UV radiation was also found to cause changes in gene expression. Genes that are related to cellular defense got more active, which seems to ensure the cell's survival under stress. Genes that control inflammation, for example, were activated.
"What's remarkable is witnessing this intricate coordination between the 3D genome, transcription and DNA repair," said first study author Veysel Oğulcan Kaya. "What surprised us most was how quickly the DNA damage response happens: within just twelve minutes after UV exposure. Even more surprising is that we could observe early signs of recovery within the first thirty minutes."
The researchers are hopeful that these findings may lead to better treatments for skin cancer, since they shed more light on DNA repair and reorganization. It may be possible to use this data to design better drugs that trigger the body's DNA repair mechanisms.
"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."
Sources: Sabanci University, Nature Communications
