Credit: Jeroen van den Berg and Vincent van Batenburg. Copyright: Hubrecht Institute 17 June 2024 New method can determine the speed of DNA replication in individual cells Back to news Researchers have developed a new technique that allows them to determine the speed of DNA replication in individual cells. The so-called scEdU-seq method allows scientists to measure how fast the cell’s DNA-copying machinery works at different times and in different DNA regions. Using this technique, the team discovered that DNA copying is slower at sites where mRNA is produced. This technique could provide new fundamental knowledge about DNA replication and can also be applied in research on embryonic development and cancer. The study by the Van Oudenaarden group was published in Nature Methods on June 17, 2024. Our body’s cells must divide regularly to create new cells. Before a cell divides, its DNA must first be copied in a process called DNA replication. It is important that the DNA code is copied very precisely and without errors; otherwise, diseases such as cancer may arise. During DNA replication, the cell’s “copying machine” moves along the long DNA strands to duplicate them. Should the machine encounter problems along the way, it can slow down for a moment to prevent copying errors from occurring. So, it is normal for the speed of DNA replication to vary depending on the timing and the section of DNA being copied at that moment. Every cell is different Scientists do not yet fully understand why the replication rate varies by time and DNA region. This is because it is difficult to determine in detail how the replication rate changes in a single cell. Researchers from the Van Oudenaarden group have now developed a technique that makes this possible for the first time: scEdU-seq. Jeroen van den Berg, co-first author of the study, explains: “Whereas before it was only possible to study many cells simultaneously and thus get a kind of average picture of the replication rate, with this new technique we can map replication in individual cells. This makes it possible to look at the differences between cells.” Malfunctioning copying machines Using the new technique, the team discovered that certain DNA regions are copied more slowly than others. Specifically, this applied to the spots on the DNA that are currently used for protein production. This is where the genetic information on the DNA is read to produce so-called mRNA molecules, which are later used as “instructions” for making proteins. The researchers found that producing mRNA during DNA replication causes DNA damage, which in turn can slow down the DNA- copying machines. This discovery was the opposite of what the researchers had expected. “We thought that DNA replication at these sites would actually be faster rather than slower. This is because the structure of these pieces of DNA is more open and accessible because there is mRNA production going on. You would think then that the copy machines would have better and faster access to do their work,” said Vincent van Batenburg, co-first author of the study. Instead, DNA replication and mRNA production seem to get in each other’s way. New possibilities The technique offers new opportunities for other scientists who want to study the dynamics of DNA replication in individual cells. The Van Oudenaarden group would also like to expand the method so that it can be used to study DNA replication in a developing embryo or in tumor tissue. Finally, the scEdU-seq technique will soon be offered as a service to other scientists through the Hubrecht Institute’s Single-Cell Core. Publication Quantifying DNA replication speeds in single cells by scEdU-seq. Jeroen van den Berg*, Vincent van Batenburg*, Christoph Geisenberger, Rinskje B. Tjeerdsma, Anchel de Jaime-Soguero, Sergio P. Acebrón, Marcel A.T.M. van Vugt and Alexander van Oudenaarden. Nature Methods, 2024. * These authors contributed equally. Alexander van Oudenaarden is group leader at the Hubrecht Institute, professor of Quantitative Biology of Gene Regulation at UMC Utrecht and Utrecht University, and Oncode Investigator.
