3/20/2023 0 Comments Fda human protein scaffold'Roughly speaking, the difference between the proportions of the protein-scaffolding and the DNA fracture corresponds to a basketball and a pin head', says Fena Ochs.Īccording to the researchers, the fact that the supporting protein scaffold is so much bigger than the fracture, underlines how important it is for the cell to not only stabilize the DNA wound, but also the surrounding environment. However, with the help of the super-resolution microscopes, scientists were able to see that error-free repair of broken DNA requires a much larger construction. So why is this discovery so novel? The previous assumption was that proteins such as 53BP1 and RIF1 act only in the closest neighbourhood of the DNA fracture. 'This could be compared to putting a plaster cast on a broken leg it stabilizes the fracture and prevents the damage from getting worse and reaching a point where it can no longer heal,' says Postdoc Fena Ochs, from the Novo Nordisk Foundation Center for Protein Research and the first author of the new study. This technology enables researchers to zoom in on living cells and visualize objects about the size of one-thousandth of the width of a hair and follow how the protective protein scaffold assembles and grows around the DNA fracture. Highly advanced super-resolution microscopes were used in this study. This opens up an opportunity to better design how DNA damage causes disease and design drugs that improve treatment of patients with unstable DNA,' says Center Director and Professor Jiri Lukas of the Novo Nordisk Foundation Center for Protein Research. Understanding the body's natural defence mechanisms enables us to better understand how certain proteins communicate and network to repair damaged DNA. This scaffold then locally concentrates special repair proteins, that are in short supply, and that are critically needed to repair DNA without mistakes. In short, two proteins called 53BP1 and RIF1 engage to build a three-dimensional 'scaffold' around the broken DNA strands. The findings have been published in the scientific journal Nature. Now researchers from the Novo Nordisk Foundation Center for Protein Research at the University of Copenhagen have discovered how certain proteins orchestrate repair of damaged DNA to ensure its stability over generations and to prevent collateral damage to the neighbouring unharmed DNA. In turn, this can lead to irreversible genetic damage and ultimately cause diseases such as cancer, immune deficiency, dementia or developmental defects. As a result, DNA strands can be broken at least once during each cell division cycle and this frequency can increase by certain lifestyles, such as smoking, or in individuals who are born with defects in DNA repair. This is not a small task because our DNA is constantly under attack, both from the environment but also from the cell's own metabolic activities. Every day, the body's cells divide millions of times, and the maintenance of their identity requires that a mother cell passes complete genetic information to daughter cells without mistakes.
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