DNA supercoiling is a process where the DNA strand gets over- or underwound, similar to how a telephone cord can be twisted. This process affects the reading of genes, which is important for cell growth and responding to signals. Using advanced microscopy techniques to visualize the reading process in living cells, they found that when DNA supercoils accumulate, it can inhibit the reading of adjacent genes. This is because over- and underwinding of DNA throws off the factors that bind to DNA, making reading less efficient. As a result, the neighboring genes can be unable to be read properly.
The study, published in Molecular Cell, also found that in normal cells, enzymes efficiently remove over- and underwinding of DNA. However, the researchers speculate that in diseases like cancer, this removal can be disrupted, leading to deregulated gene regulation.
“This discovery is significant because it highlights a new mechanism of gene regulation in cells, and provides a new way to understand how coordination between genes is established,” said researcher Tineke Lenstra. “By understanding how overwinding and underwinding can impact neighboring genes during the transcription process, we can work towards better understanding the deregulation of gene expression in cancer cells and how to treat it.”
The study also has potential implications for the interplay between the reading of genes and DNA repair processes, as over- and underwinding occurs during other processes on DNA, such as DNA repair after damage. Genes near the damage could also be inhibited in a similar way, highlighting the importance of timely and efficient removal of overwinding and underwinding by enzymes.
Overall, this study provides new insights into how genes are regulated and highlights the importance of proper coordination of multiple gene reading. The findings could have significant implications for our understanding of diseases like cancer and could pave the way for new therapies that target the removal of DNA supercoils to prevent deregulated gene regulation.