A new study by Professor Jo Morris from the University of Birmingham identified a protein called USP50 that plays a crucial role in DNA replication by helping determine which enzymes cut or unwind DNA during the process.
Scientists found that USP50 assists in selecting the appropriate nucleases and helicases—enzymes essential for DNA replication, especially when the replication machinery encounters problems and needs to restart.
USP50 helps explicitly regulate the use of these enzymes during ongoing replication, fork restarts, and the maintenance of telomeres, which are the DNA-rich structures at the ends of chromosomes. Understanding USP50’s role offers new insights into the DNA replication process and could help explain the development of certain hereditary conditions.
Professor Morris stated that their study focuses on how cells regulate the use of specific enzymes for DNA replication. With multiple enzymes involved in cutting and unwinding DNA, cells must choose which ones to use to ensure proper replication. This discovery could be a significant step toward understanding how genetic changes can lead to early aging and cancer.
One of the greatest mysteries of DNA replication has been solved
The study also revealed that when USP50 is missing during DNA replication, cells struggle to coordinate using different nucleases and helicases, leading to replication defects.
Professor Morris noted that it was surprising to find that cellular nucleases and helicases could halt replication in some regions of DNA. This finding emphasizes how important it is for cells to carefully coordinate their collection of DNA-processing enzymes to ensure successful DNA replication.
Professor Simon Reed, Co-Director of the Division of Cancer and Genetics at Cardiff University, a co-founder of Broken String Biosciences, and co-author of the paper, said:
“I am truly honored to have co-authored this paper published in Nature Communications, exploring the critical role of USP50 in safeguarding genome stability. This research sheds light on the complex mechanisms that protect our cells from DNA damage and highlights how these discoveries could shape future therapies. Thank you to my collaborators—together, we’ve taken another step forward in understanding how our cells function and how we can apply this knowledge to advance medical science.”
Journal Reference:
- Mackay, H.L., Stone, H.R., Ronson, G.E. et al. USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication. Nat Commun 15, 8102 (2024). DOI: 10.1038/s41467-024-52250-4
