Irvine, Calif., Jan. 6, 2025 — A research team from the University of California, Irvine has revealed a previously unknown mechanism that triggers an inflammatory immune response in cells when their DNA is damaged. This discovery deepens the understanding of a new type of cell signaling that may lead to more effective treatments for cancer.
The study, published online today in the journal Nature Structural & Molecular Biology, found that UV irradiation or certain chemotherapeutic drugs activate a specific response when cells are too damaged to be repaired correctly, preventing them from becoming cancerous.
“This discovery could have significant implications for cancer treatment,” said corresponding author Rémi Buisson, UC Irvine associate professor of biological chemistry. “Understanding how different cancer cells react to DNA damage could lead to more tailored and effective therapies, potentially reducing negative side effects and improving the quality of life for patients.”
Scientists have long understood that when both DNA strands are broken, the ATM enzyme triggers the activation of the protein NF-κB within the cell, leading to the production of inflammatory signals. In this study, spearheaded by postdoctoral fellow Elodie Bournique and assisted by graduate student Ambrocio Sanchez, it was shown that when DNA damage occurs due to UV exposure or treatment with chemotherapeutic drugs such as actinomycin D or camptothecin, the IRAK1 enzyme induces NF-κB to send out signals to recruit immune cells.
Team members developed an advanced imaging technique to analyze how NF-κB is regulated at the cellular level. The researchers were able to precisely measure a cell’s response to damaged DNA at the single-cell level and observed a new pathway to the activation of NF-κB. They found that after specific types of injury, cells release the IL-1α protein. It doesn’t act on the cell itself but travels to neighboring cells, where it triggers the IRAK1 protein, which then initiates the NF-κB inflammatory response.