Using the method of precise genome mapping, biologists recorded that the damage is not random.
Researchers from the Hebrew University of Jerusalem have shown that the hyperactivity of genes that drive rapid tumor growth leads to damage and breaks in the DNA structure of cancer cells.
The aggressive development of oncological diseases is directly related to the work of so-called super-enhancers. These DNA regions act as switches, pushing essential genes to operate at full capacity, accelerating cell division.
A new study published in the journal Science Advances shows that the high growth rate comes at a significant cost to tumor cells. Scientists found that the physical stress arising from extreme gene activity causes double-strand breaks in DNA precisely at the points where the load is maximal.
Using the method of precise genome mapping, biologists recorded that the damage is not random: it concentrates in the areas influenced by super-enhancers. The cell recognizes these breaks and initiates repair mechanisms, but the constant cycle of destruction and repair inevitably leads to the accumulation of errors.
Such "hot spots" become sources of new mutations that allow tumors to evolve, adapt to therapy, and become even more aggressive. As the researchers demonstrated, the mechanism that gives cancer the strength to grow simultaneously makes it genetically unstable and potentially vulnerable.
Professor Rami Akil, who led the study, says: "Cancer cells rely on super-enhancers to maintain a high rate of growth gene activity. We found that this same activity creates a real burden on DNA, creating break points that the cell has to repair over and over again. This cycle helps tumors survive in the short term, and it also increases the risk of mutations that affect cancer evolution."
Understanding this process opens new prospects for medicine. Since cancer cells critically depend on these high-stress zones, therapies aimed at disrupting DNA repair mechanisms or suppressing super-enhancer activity could become effective ways to combat the most resistant forms of the disease.
