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08-20-2024

Protein that halts DNA damage may lead to cancer vaccines

Every so often in the world of scientific discovery, a finding like the DdrC protein emerges with the potential to revolutionize various fields of life.

Researchers at Western University have identified this remarkable molecule, which could ultimately form the basis for cancer vaccines and climate-resilient crops.

The resilient DNA defense trooper

The experts at Western University discovered the DNA Damage Repair Protein C (DdrC) in the bacterium Deinococcus radiodurans.

This particular bacterium has the incredible ability to survive conditions that would normally be catastrophic to DNA, thriving even under 5,000 to 10,000 times the radiation that would wipe out an ordinary human cell.

Lead researcher Robert Szabla, a graduate student in Western’s Department of Biochemistry, noted that Deinococcus also excels in repairing DNA that has already been damaged. The study has now revealed that DdrC is a crucial player in this repair process.

“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,” said Szabla.

The remarkable capabilities of the DdrC protein

Every cell in the body is equipped with a DNA repair mechanism to rectify damage. “With a human cell, if there are any more than two breaks in the entire billion base pair genome, it can’t fix itself and it dies,” said Szabla. “But in the case of DdrC, this unique protein helps the cell to repair hundreds of broken DNA fragments into a coherent genome.”

The team further analyzed the structure of the protein using the Canadian Light Source (CLS) at the University of Saskatchewan. This process helped them comprehend the protein’s “superpower” to counteract DNA damage.

“The Canadian Light Source was instrumental in that,” said Szabla. “It’s the most powerful X-ray source in Canada.”

Scanning for DNA damage

The function of DdrC is likened to a mousetrap, scanning for breaks in the DNA and snapping shut when one is detected.

This, according to Szabla, has two key functions: “It neutralizes it (the DNA damage) and prevents the break from getting damaged further. And it acts like a little molecular beacon. It tells the cell ‘Hey, over here. There’s damage. Come fix it.'”

Unlike most proteins, DdrC operates as a lone ranger, needing no other proteins to carry out its powerful function.

The researchers were curious whether this protein might serve as an add-on for other DNA repair systems. To test this, they introduced DdrC to E. coli, and surprisingly, it made the bacterium over 40 times more resistant to UV radiation damage.

“This seems to be a rare example where you have one protein and it really is like a standalone machine,” noted Szabla.

The boundless potential of the DdrC protein

In theory, the DdrC gene can be inserted into any organism, boosting the DNA repair efficiency of that organism’s cells.

“The ability to rearrange and edit and manipulate DNA in specific ways is the holy grail in biotechnology,” said Szabla.

“What if you had a scanning system such as DdrC patrolling your cells and neutralizing damage when it happened? This might form the basis of a potential cancer vaccine.”

According to Szabla, further exploration of DdrC and Deinococcus is needed “DdrC is just one of hundreds of potentially useful proteins in this bacterium,” he noted.

“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.”

The experts at Western University are just beginning to unravel the mysteries and potential of Deinococcus and its unique protein, DdrC.

Their pioneering work has opened up new possibilities in DNA research, heralding an era of advancements that may reshape our world for the better.

The study is published in the journal Nucleic Acids Research.

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