How damaged DNA repairs
Image: Fena Ochs, Novo Nordisk Foundation Center for Protein Research, uses structured illumination microscopy to study DNA repair.
Using super-resolution microscopy, a pan-European team of researchers has made an extraordinary discovery in how the body repairs damaged DNA.
Researchers from the Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, as well as the European Biology Laboratory in Heidelberg and the University of Oxford, have discovered how proteins stabilise damaged DNA and thereby preserve DNA function and integrity of our bodies.
The new finding helps to explain why people with inherited or acquired defects in certain proteins cannot keep their DNA stable and develop diseases, such as cancer.
While cells are designed to monitor and repair DNA to protect the organism from permanent damage, flaws in these mechanisms can be disastrous and are a hallmark of many types of cancer.
To study how damaged DNA is repaired, the researchers first broke DNA strands using X-ray irradiation.
Then using confocal imaging and super-resolution microscopy, including 3D structured illumination microscopy and stimulated emission depletion microscopy, they were able to observe DNA repair.
Analyses revealed that when DNA strands break, two proteins called 53BP1 and RIF1 engage to build a 3D ‘scaffold’ around the broken strands.
Other proteins from the so-called Shieldin network are then attracted to actually repair the damage.
Defects in the 3D-stabilising process can lead to DNA damage running wild before it can be repaired.
DNA damage explanation.
“Super-resolution microscopy enabled us to zoom in on living cells and... follow how the protein scaffold assembles and grows around the DNA fracture,” highlights Dr Fena Ochs from the Novo Nordisk Foundation Center.
“Investigating the body’s natural defence mechanisms enables us to better understand how certain proteins communicate and network to repair damaged DNA,” adds Professor Jiri Lukas, Center Director at the Novo Nordisk Foundation Center. “This opens up an opportunity to learn more about why and how DNA damage causes disease and design drugs that improve treatment of patients with unstable DNA.”
The researchers will now look more closely at all the relevant proteins that repair the DNA damage with a view to creating drug resistance in the longer term.
Research is published in Nature.