OCT 28, 2019 8:26 PM PDT

Super-Resolution Microscopy Reveals How DNA Damage is Repaired

WRITTEN BY: Carmen Leitch

Our bodies replace millions of cells every day; to do so, a cell has to divide into two new daughter cells. The process requires replicating the entire genome and dividing the DNA correctly between the two new cells. Our genome can get damaged as this happens, but it can also acquire damage from many different environmental influences. Scientists have now discovered how two proteins can stabilize DNA that’s been damaged, and protect the integrity of the genome in the process. Their work, which has been reported in Nature, also shows how people that carry defects in some proteins are more susceptible to disorders like cancer, dementia, or immune problems because they can’t maintain stability in their genome or repair damaged portions.

Two proteins, 53BP1 and RIF1, were found to generate a three-dimensional scaffold around DNA strands that have broken. This scaffolding concentrates scarce repair proteins, and the critical work of DNA repair can then begin. This ensures that DNA stays stable, and prevents more damage from occurring in the surrounding area.

“It's a unique discovery. Understanding the body's natural defense mechanisms enables us to better understand how certain proteins communicate and network to repair damaged DNA. This opens up an opportunity to better design how DNA damage causes disease and design drugs that improve treatment of patients with unstable DNA,” said study co-author Professor Jiri Lukas, Center Director at the Novo Nordisk Foundation Center for Protein Research.

In this study, the researchers applied cutting-edge super-resolution microscopy that enabled them to visualize the protein scaffold as it assembled around the DNA break.

“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,” said the first author of the study, postdoctoral fellow Fena Ochs, of the Novo Nordisk Foundation Center for Protein Research.

It had been thought that these proteins were only acting in the area where DNA strands were broken. Their investigation allowed the researchers to see the large structure that 53BP1 and RIF1 formed around the breaks.

“Roughly speaking, the difference between the proportions of the protein-scaffolding and the DNA fracture corresponds to a basketball and a pinhead,” Ochs noted.

The researchers suggested that the protein scaffold shows that the DNA break must be stabilized, and so does the area around it. The damaged area is this preserved, there is less of a chance that more damage will occur, and the special proteins doing the repair, members of the shieldin network, can do their jobs.

When the scaffolding proteins were removed, the researchers saw that large sections of the chromosome around the break rapidly fell apart. When the scaffolding proteins are absent, cancer can arise, because although the cells attempt to fix the problem, the effort is futile. People that don’t carry functional copies of these proteins are more likely to get diseases that arise from unstable DNA.


Sources: AAAS/Eurekalert! via University of Copenhagen, Nature

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
MAY 10, 2021
Genetics & Genomics
DNA Supercoiling is Found to Play a Role in Gene Expression
MAY 10, 2021
DNA Supercoiling is Found to Play a Role in Gene Expression
A cell has many ways to control gene expression, one of which is the structure of the genome itself; active genes have t ...
MAY 18, 2021
Genetics & Genomics
The Oral Microbiome Reveals How Long We've Loved Starchy Foods
MAY 18, 2021
The Oral Microbiome Reveals How Long We've Loved Starchy Foods
Bacteria are everywhere, including our guts and mouths. Researchers are learnings more about the history of the human mi ...
MAY 19, 2021
Genetics & Genomics
The Genetic Secrets of Long-Lived People
MAY 19, 2021
The Genetic Secrets of Long-Lived People
For 2019, the United Nations estimated that the average life expectancy for a person is 72.6 years of age. People that l ...
MAY 19, 2021
Health & Medicine
Who Ages Better, Men or Women?
MAY 19, 2021
Who Ages Better, Men or Women?
The answer depends on what's considered more important – quantity or quality of years?  Previous studies ...
JUL 15, 2021
Cell & Molecular Biology
Do Microbial Pathogens Have an Epigenetic Memory?
JUL 15, 2021
Do Microbial Pathogens Have an Epigenetic Memory?
Epigenetics are the parts of the genome that can affect the activity of genes but don't involve making changes to th ...
JUL 20, 2021
Cell & Molecular Biology
Do Phages Drive Bacterial Evolution?
JUL 20, 2021
Do Phages Drive Bacterial Evolution?
Antibiotics are a standard treatment for bacterial infections, but more and more of these bacterial infections can't be ...
Loading Comments...