Newly Discovered Protein Stops DNA Damage

Researchers at Western University have discovered a protein with the unprecedented ability to stop DNA damage. The discovery could provide the basis for developing everything from cancer vaccines to crops that can withstand the increasingly harsh growing conditions brought on by climate change.

The researchers discovered the protein, called DdrC (for DNA Damage Repair Protein C), in a relatively common bacterium called Deinococcus radiodurans (D. radiodurans), which has the unusual ability to survive conditions that damage DNA, such as radiation 5,000 to 10,000 times higher than what would kill a normal human cell. Lead researcher Robert Szabla explains that Deinococcus is also excellent at repairing already damaged DNA.

“It’s like having an NFL player who plays every game without a helmet or pads,” says Szabla, a graduate student in Western’s biochemistry department. “He’d end up with a concussion and multiple fractures every game, but he’d miraculously make a full recovery overnight in time for practice the next day.” He and his colleagues have discovered that DdrC plays a key role in this repair process.

Every cell has a DNA repair mechanism to fix damage. “In the case of a human cell, if there are more than two breaks in the entire billion-base-pair genome, it can’t repair itself and it dies,” he explains. “But in the case of DdrC, this single protein helps the cell repair hundreds of broken DNA fragments into a coherent genome.”

Szabla and his team used the Canadian Light Source (CLS) at the University of Saskatchewan (USask) to determine the 3D shape of the protein, from which they then worked backwards to better understand its “superpower” of neutralizing DNA damage.

“The Canadian Radiation Source was instrumental in this process,” Szabla says. “It’s the most powerful X-ray source in Canada.” The group’s results were published in the journal Nucleic Acid Research.

It turns out that DdrC looks for breaks along the DNA, and when it detects one, it snaps shut, like a mousetrap. This trapping action has two key functions. He explains: “It neutralizes 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.’”

Typically, Szabla explains, proteins form complex networks that allow them to perform a function. The DdrC protein appears to be an exception, in that it performs its function on its own, without the need for other proteins. The team wondered whether this protein could function as a “plug-in” for other DNA repair systems.

They tested this method by adding it to another bacterium: E. coli. “To our surprise, this protein made the bacterium 40 times more resistant to UV damage,” he says. “This seems to be a rare example of a single protein functioning as a stand-alone machine.”

He says that in theory, this gene could be introduced into any organism (plants, animals, humans) and it should increase the efficiency of DNA repair in that organism’s cells.

“The ability to rearrange, modify and manipulate DNA in specific ways is the holy grail of biotechnology,” Szabla says. “What if you had a scanning system like DdrC that patrolled your cells and neutralized damage when it occurred? That could be the basis of a potential cancer vaccine.”

The Western team has only just begun studying Deinococcus. “DdrC is just one of hundreds of potentially useful proteins in this bacterium. The next step is to go further and see what else this cell uses to repair its own genome, because we’re sure to find many other tools that we don’t know how they work or what they’ll be useful for until we study them,” he concludes.