Researchers Find ‘Protein-Scaffolding’ for Repairing DNA Damage
At the University of Copenhagen, researchers have discovered how some types of proteins stabilize damaged DNA and thereby preserve DNA function and integrity. This new finding also explains why people with inborn or acquired defects in certain proteins cannot keep their DNA stable and develop diseases such as cancer.
Facts: DNA damage and repair
DNA is the template of life and contains the recipe for our body’s building blocks, the proteins.
In humans, a DNA molecule is approximately 2 metres long when uncoiled but is presently compressed in the nucleus of every cell.
Every day, both internal and external factors damage the DNA in our cells. The worst damages are the so-called DNA double-strand break fractures, where both ends of the DNA break apart.
Fortunately, our cells are designed to monitor, care for and repair the DNA to protect the organism from permanent damage.
Flaws in these mechanisms can be disastrous and are a hallmark of many types of cancer.
Researchers from the University of Copenhagen have now demonstrated that DNA damage in normal cells is quickly stabilised by the proteins 53BP1 and RIF1. Other proteins from the so-called Shieldin network are then attracted to actually repair the damage.
Defects in the 3D-stabilizing process can lead to DNA damage running wild before it can be repaired.
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.
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. 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.
In turn, this can lead to irreversible genetic damage and ultimately cause diseases such as cancer, immune deficiency, dementia or developmental defects.
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 short, two proteins called 53BP1 and RIF1 engage to build a three-dimensional ‘scaffold’ around the broken DNA strands. This scaffold then locally concentrates special repair proteins, that are in short supply, and that are critically needed to repair DNA without mistakes.