Researchers from Western University have discovered a protein that has the never-before-seen ability to stop DNA damage in its tracks. (Credit: Canadian Light Source)

LONDON, Ontario — Scientists at Western University may have just discovered the ultimate bodyguard for your DNA. They’ve found a protein with an extraordinary ability to halt DNA damage in its tracks, and it could be a game-changer for everything from cancer prevention to crop resilience.

Imagine a tiny superhero patrolling your cells, ready to swoop in and save the day whenever your DNA is in danger. That’s essentially what this newly discovered protein, called DdrC (DNA Damage Repair Protein C), does. According to the findings in Nucleic Acids Research, it comes from a fascinating bacterium with an equally fascinating name: Deinococcus radiodurans.

What makes D. radiodurans so special?

This little microbe is practically indestructible when it comes to DNA damage. It can withstand radiation levels 5,000 to 10,000 times stronger than what would kill a human cell. But that’s not all – it’s also incredibly good at repairing DNA that’s already been damaged.

“It’s as if you had a player in the NFL who plays every game without a helmet or pads,” says Robert Szabla, the study’s lead researcher, in a media release. “He’d end up with a concussion and multiple broken bones every single game, but then miraculously make a full recovery overnight in time for practice the next day.”

So, what exactly does DdrC do? Think of it as a highly specialized security system for your genetic material. It constantly scans along the DNA, looking for any signs of damage. When it finds a break, it snaps into action – literally. The protein clamps down on the damaged area, much like a mousetrap.

This swift response serves two crucial purposes:

1. It stops the damage from getting worse, kind of like applying a bandage to prevent further injury.
2. It acts as a beacon, signaling to the cell’s repair crew that there’s a problem that needs fixing.

What’s truly remarkable about DdrC is that it seems to work all on its own. Most proteins in our cells need to team up with others to get things done, but DdrC is like a one-protein army.

The researchers were curious to see if DdrC could lend its superpowers to other organisms. They introduced it to E. coli, a common bacterium often used in lab experiments. The results were astounding – the E. coli became over 40 times more resistant to UV radiation damage! This discovery opens up a world of possibilities.

Szabla explains that, in theory, this gene could be introduced into any organism – plants, animals, humans – and it would increase that living being’s ability to repair its DNA.

Imagine the potential applications:

• A “vaccine” against cancer by boosting our cells’ ability to prevent DNA damage
• Crops that can withstand harsh conditions brought on by climate change
• New treatments for diseases caused by DNA damage

‘The Holy Grail in biotechnology’

“The ability to rearrange and edit and manipulate DNA in specific ways is the holy grail in biotechnology,” says Szabla. “What if you had a scanning system such as DdrC which patrolled your cells and neutralized damage when it happened? This might form the basis of a potential cancer vaccine.”

However, DdrC might just be the tip of the iceberg. The researchers believe there could be hundreds more useful proteins waiting to be discovered in D. radiodurans. Each one could potentially unlock new ways to protect and repair DNA, leading to breakthroughs we can’t even imagine yet.

This groundbreaking research wouldn’t have been possible without some seriously high-tech equipment. The team used the Canadian Light Source (CLS) at the University of Saskatchewan, which Szabla describes as “the most powerful X-ray source in Canada.”

This advanced technology allowed the scientists to determine the 3D shape of the DdrC protein. From there, they could work backwards to understand how it performs its DNA-protecting “superpower.”

While the discovery of DdrC is exciting, it’s important to remember that scientists are still in the early stages of understanding its full potential. There’s a lot more work to be done before we might see applications in medicine or agriculture.

“DdrC is just one out of hundreds of potentially useful proteins in this bacterium. The next step is to prod further, look at what else this cell uses to fix its own genome – because we’re sure to find many more tools where we have no idea how they work or how they’re going to be useful until we look,” Szabla concludes.

Paper Summary

Methodology

To understand how DdrC works, the researchers conducted a series of experiments that included crystallography to study the protein’s structure, and various biochemical assays to test its ability to bind and compact DNA. The crystallography revealed the unusual asymmetric structure of DdrC, while the biochemical assays showed how DdrC interacts with DNA to stabilize and repair it.

In one set of experiments, the researchers used different types of DNA, including linear DNA with single and double breaks, to see how DdrC would respond. They found that DdrC was most effective at compacting DNA when there were multiple breaks, confirming that the protein’s compaction ability is linked to the extent of DNA damage.

Key Results

DdrC was shown to bind to DNA at the site of breaks and induce compaction by bringing the broken ends closer together. This compaction was most pronounced when there were multiple breaks, and it led to the circularization of linear DNA. This circularization is a crucial step in the DNA repair process, as it allows the broken ends to be rejoined more easily.

The researchers also found that DdrC’s ability to compact DNA was dependent on its asymmetrical structure. Without this asymmetry, the protein could not bind to multiple breaks simultaneously, and the DNA could not be compacted or circularized effectively.

Study Limitations

While the study provides important insights into how DdrC repairs DNA, there are still many questions to be answered. For example, the exact mechanism by which DdrC recognizes DNA breaks is not fully understood. Additionally, while the protein’s ability to compact DNA is clear, the researchers were not able to determine whether DdrC actively supercoils the DNA or simply induces a similar structure.

Further research will be necessary to explore these questions, as well as to determine whether similar proteins exist in other organisms. The findings also raise the possibility that DdrC could be used in biotechnological applications, such as developing new methods for repairing damaged DNA in human cells or protecting DNA during long-term space missions.

Discussion & Takeaways

The discovery of DdrC’s unique mechanism for repairing DNA is a significant advancement in our understanding of how D. radiodurans survives in extreme conditions. By compacting and stabilizing DNA, DdrC ensures that the bacterium’s genetic material remains intact, even in the face of severe damage. This ability could have important implications for a variety of fields, including medicine, biotechnology, and space exploration.

One of the key takeaways from this study is the importance of protein structure in DNA repair. DdrC’s asymmetry allows it to perform a function that would be impossible for a symmetric protein, highlighting the role that protein structure plays in biological processes.

Funding & Disclosures

This research was supported by funding from the Natural Sciences and Engineering Research Council of Canada. The authors declare no competing interests related to this study.

Source: StudyFinds