A team of scientists, led by N2CR member Dr. Tee Wee Wei, has identified the enzyme DNA topoisomerase I (TOP1) as a key regulator of gene activity crucial for normal development and health. Their discovery reveals that a specific disease-associated mutation (R548Q) in TOP1 accelerates gene activity, disrupting normal developmental programs. Tight control of gene activity is essential, as dysregulation can contribute to diseases, particularly in aggressive cancers characterized by transcriptional overdrive. Importantly, the mutation does not impact TOP1’s primary enzymatic function but hinders its ability to bind to DNA correctly. This research highlights TOP1 as a molecular rheostat, ensuring precise control of gene activity levels and maintaining appropriate total transcription levels in our cells.

Read more here: https://www.nature.com/articles/s41467-023-42078-9