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 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
MAR 09, 2020
Genetics & Genomics
MAR 09, 2020
Researchers Alter How Bacteria Communicate
The bacterium Escherichia coli comes in many forms, and researchers have used a harmless strain of it to redesign how th ...
APR 05, 2020
Genetics & Genomics
APR 05, 2020
Gene Variants Impact Natural Sunscreen & Vitamin D Levels
Vitamin D deficiencies have been linked to a variety of chronic diseases including bone disorders and heart disease.
APR 12, 2020
Genetics & Genomics
APR 12, 2020
Even Brief Exposure to Air Pollution Can Affect Gene Expression
Studies in mice and humans have shown that the negative health effects of pollution are accompanied by changes in gene e ...
APR 13, 2020
Cell & Molecular Biology
APR 13, 2020
Getting Closer to Making Heparin in Cells
While heparin is the most commonly prescribed drug in hospitals, we have to extract it from pig intestines, which is fra ...
MAY 06, 2020
Cardiology
MAY 06, 2020
Can Alcohol Consumption Increase Your Risk of Peripheral Arterial Disease?
Peripheral Arterial Disease (PAD) is a chronic disease where plaque builds up in the arteries in the legs. This buildup ...
MAY 19, 2020
Cancer
MAY 19, 2020
Great ape genomes closer to human tumors than human genomes
A new study analyzing cancer from an evolutionary perspective reports that the distribution of mutations in human tumors ...
Loading Comments...