A study published in the journal Nucleic Acids Research by Western University reports discovering a protein that has the ability to stop DNA damage. This discovery could be the holy grail for developing everything from DNA repair to crop resilience and cancer prevention.
The protein is called DdrC (DNA Damage Repair Protein C) and it comes from the bacterium Deinococcus radiodurans which has the uncommon ability to survive extreme conditions that damage DNA such as surviving 5,000 to 10,000 times the radiation that would kill a regular human cell. According to lead researcher Robert Szabla, Deinococcus also excels in repairing DNA that has already been damaged.
“It’s as if you had a player in the NFL who plays every game without a helmet or pads,” says Szabla, a grad student in Western’s Department of Biochemistry. “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.”
“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,” says Szabla. “But in the case of DdrC, this unique protein helps the cell to repair hundreds of broken DNA fragments into a coherent genome.”
Decidedly Uncommon Abilities
For this study, the researchers used the Canadian Light Source (CLS) at the University of Saskatchewan to investigate the 3D shape of the protein and then worked backward to study the amazing ability to neutralize DNA damage.
“The Canadian Light Source was instrumental in that,” says Szabla. “It’s the most powerful X-ray source in Canada.”
DdrC appears to scan for breaks in DNA, and when one is found it closes in like a trap, and this action seems to have two 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.”
The researchers explained that proteins will typically form complicated networks that enable them to carry out a function. However, DdrC appears to be an outlier, in that it performs its function all on its own, without the need for other proteins.
The Holy Grail in Biotechnology
The researchers also tested whether or not the protein might function as a “plug-in” for other DNA repair systems 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,” said Szabla. “This seems to be a rare example where you have one protein, and it really is like a standalone machine.”
While the research has only just begun on this amazing discovery, there are still many questions to be answered, but the implications are vast. For example, in theory, this means that this gene could be integrated into any organism from plants to animals and humans and it could increase the efficiency of DNA repair in that organism’s cells.
“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.”
“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.”
Accompanying video via CLS: https://www.youtube.com/watch?v=_uMTHA4HZb4
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Image Credit: The Canadian Light Source
https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkae635/7717837