Researchers have discovered a protein that has the never-before-seen ability to halt DNA damage. This finding could provide the foundation for developing everything from vaccines against cancer, to crops that can withstand climate change.
DNA Damage Repair Protein C (DdrC), shown from two different angles. Credit: R. Szabla, et al. Nucleic Acids Research (2024)
Scientists have identified a new protein called DNA Damage Repair Protein C (DdrC), which exists within Deinococcus radiodurans. This fairly common bacterium (pictured below) can survive conditions that would normally damage or destroy DNA. It will tolerate between 5,000 and 10,000 times the radiation dose needed to kill a regular human cell, for example, making it one of the most radiation-resistant organisms known to science. Deinococcus also excels at repairing DNA that has already been damaged.
The protein DdrC is described this month in Nucleic Acids Research. "It's as if you had a player in the NFL who plays every game without a helmet or pads," explains Robert Szabla, a grad student at Western University's Department of Biochemistry, and one of the study authors. "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."
The bacterium Deinococcus radiodurans, which contains the DdrC protein.
Szabla and his team used the Canadian Light Source (CLS), a particle accelerator housed at the University of Saskatchewan (USask), to determine the 3D shape of the protein, from which they then worked backwards to better understand its remarkable abilities. "The Canadian Light Source was instrumental in that," explains Szabla. "It's the most powerful X-ray source in Canada."
Every cell has a DNA repair mechanism to fix 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. But in the case of DdrC, this unique protein helps the cell to repair hundreds of broken DNA fragments into a coherent genome," says Szabla.
DdrC alongside a DNA strand. Credit: R. Szabla, et al. Nucleic Acids Research (2024)
As shown in the diagram above, DdrC glides along the DNA strand, scanning for breaks. When it detects one it snaps shut – like a mousetrap. This trapping action serves two key functions: "It neutralises 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, says Szabla, proteins form complicated networks that enable them to carry out a function. DdrC appears to be something of an outlier, in that it performs its function all on its own, without the need for other proteins. The team was curious whether the protein might function as a "plug-in" for other DNA repair systems. They tested this by adding it to a different bacterium: E. coli. "To our huge surprise, it actually made the bacterium over 40 times more resistant to UV radiation damage," he says. "This seems to be a rare example where you have one protein, and it really is like a standalone machine."
He says that, in theory, this gene could be introduced into any organism – plants, animals, humans – and it should increase the DNA repair efficiency of that organism's cells. "The ability to rearrange, edit, and manipulate DNA in specific ways is the holy grail in biotechnology," Szabla continues. "What if you had a scanning system like DdrC which patrolled your cells and neutralised damage when it happened? This might form the basis of a potential cancer vaccine."
The Western team is just getting started studying Deinococcus. "DdrC is just one out of hundreds of potentially useful proteins in this bacterium. The next step is to prod further and 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."
By futureTimeLine
