Researchers from Western University in Ontario, Canada, have made a groundbreaking discovery that could revolutionize the fields of medicine and agriculture. They have identified a unique protein called DdrC, which has the unprecedented ability to halt DNA damage in its tracks. This discovery, centered around the protein found in the resilient bacterium Deinococcus radiodurans, could potentially pave the way for innovations ranging from cancer vaccines to drought-resistant crops.
The bacterium Deinococcus radiodurans, from which the DdrC protein was isolated, is known for its remarkable ability to endure extreme conditions that cause DNA damage. This microorganism can survive radiation levels 5,000 to 10,000 times higher than what would be fatal to human cells. As lead researcher Robert Szabla, a graduate student in Western’s Department of Biochemistry, puts it, “It’s as if you had a player in the NFL who plays every game without a helmet or pads… 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.” Szabla and his team found that DdrC plays a key role in Deinococcus’s unique DNA repair system, which allows the bacterium to survive such extreme damage.
In most organisms, DNA repair mechanisms are limited. Human cells, for instance, can typically only repair a couple of DNA breaks in their genome at a time. If there are more than two breaks, the cell usually cannot fix itself and dies. However, Deinococcus and its DdrC protein are capable of repairing hundreds of fragmented pieces of DNA, reassembling them into a functional genome. “This unique protein helps the cell to repair hundreds of broken DNA fragments into a coherent genome,” Szabla said in a news release, highlighting the exceptional power of DdrC.
To understand how DdrC works, Szabla and his team employed Canada’s most powerful X-ray source, located at the Canadian Light Source in Saskatchewan. By analyzing the protein’s 3D structure, the researchers gained insight into its remarkable ability to stop DNA damage. They discovered that DdrC scans the DNA for breaks, and upon detecting one, it snaps shut—much like a mousetrap. This action has two primary effects: it halts further damage to the DNA and signals to the cell that there is an issue that needs to be addressed. “It neutralizes the DNA damage, and it acts like a little molecular beacon. It tells the cell ‘Hey, over here. There’s damage. Come fix it,’” Szabla explains.
Most proteins involved in DNA repair form complex networks and require assistance from other proteins to perform their functions. However, DdrC is different in that it operates independently. This self-sufficiency, Szabla notes, is highly unusual. “It performs its function all on its own, without the need for other proteins,” he said.
Intrigued by the possibility of applying DdrC’s DNA repair abilities beyond Deinococcus, the research team tested the protein in Escherichia coli (E. coli), a different bacterium. To their astonishment, adding DdrC made E. coli more than 40 times more resistant to UV radiation damage. The results, published in the journal Nucleic Acids Research, indicate that this is a rare instance where a single protein functions as a complete, standalone machine. “This seems to be a rare example where you have one protein, and it really is like a standalone machine,” Szabla said.
The potential applications of this discovery are vast. In theory, the DdrC gene could be introduced into any organism—plants, animals, or humans—to enhance the efficiency of DNA repair within cells. “The ability to rearrange and edit and manipulate DNA in specific ways is the holy grail in biotechnology,” Szabla remarked. He believes that if a system like DdrC could be integrated into human cells, it might form the foundation of a potential cancer vaccine, patrolling cells and neutralizing DNA damage before it becomes cancerous.
The discovery of DdrC is only the beginning for Szabla and his team, who believe there are more valuable proteins waiting to be found in Deinococcus radiodurans. “DdrC is just one out of hundreds of potentially useful proteins in this bacterium,” he said. “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 is particularly optimistic about the future of cancer prevention. “Currently, when we think of cancer treatments, we always think of treating it once it’s already happened. What if we can prevent the cancer from happening in the first place?” he asked. The discovery of DdrC could be the key to unlocking that possibility, offering hope for a future where cells can be repaired before cancer ever takes root.
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