Researchers at Western University have discovered a protein with an unprecedented ability to stop DNA damage in its tracks, a discovery that could pave the way for everything from cancer vaccines to crops that can withstand increasingly severe droughts.
Researchers in Ontario, Canada, have discovered a protein called DNA damage repair protein C (DdrC) in the common bacterium Deinococcus radiodurans. The bacterium has a rare ability to survive in environments that damage its DNA. The protein can withstand radiation that is 5,000 to 10,000 times stronger than the radiation that kills normal human cells.
Deinococcus also appears to be very effective at repairing already damaged DNA, said lead researcher Robert Sabla.
“It’s like an NFL player playing every game without a helmet or pads,” says Szabla, a graduate student in biochemistry at Western.
“He suffered a concussion and multiple broken bones in each game, but miraculously made a full recovery overnight in time for practice the next day.” He and his teammates discovered that DdrC plays a key role in this repair process.
All cells have DNA repair mechanisms to repair damage. “In a human cell, if there are two or more breaks in the entire billion-base-pair genome, it cannot repair itself and it dies,” he said in a press release.
“But in the case of DdrC, this unique protein helps cells repair hundreds of broken pieces of DNA into a coherent genome.”
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Sabla and his team used the most powerful X-rays in the country, at the Canadian Light Source at the University of Saskatchewan in Canada, to map out the protein’s 3D shape and then work backwards from there to better understand the protein’s “superpowers” in neutralizing DNA damage.
They found that DdrC scans for breaks along the DNA and, when it detects a break, closes like a mousetrap. This trapping behavior has two main functions.
“It neutralizes DNA damage, it prevents further damage, and it acts like a little molecular signal that says to the cell, ‘Hey, I’m here. There’s damage. Come and fix it.'”
Typically, proteins form complex networks to perform their functions, says Szabla. DdrC seems to be somewhat of an outlier in that it performs its function on its own, without the need for other proteins.
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The team also wondered whether this protein could function as a “plug-in” for other DNA repair systems. They tested it by adding it to another bacterium, E. coli.
“What was really surprising to us was that the bacteria actually became more than 40 times more resistant to UV damage,” he reported in the journal Nucleic Acids Research. “This seems to be a rare example of a single protein that is actually a standalone machine.”
He said that in theory, this gene could be introduced into any organism – plants, animals, humans – and it would increase the efficiency of DNA repair in that organism’s cells.
“The ability to rearrange, edit and manipulate DNA in specific ways is the holy grail of biotechnology,” says Sabla. “What if we had a scanning system like DdrC that patrolled the cell and neutralized damage when it occurred? This could form the basis of a potential cancer vaccine.”
The Western team has just started researching Deinococcus.
“DdrC is just one of hundreds of potentially useful proteins in this bacterium. The next step is to go further and look at the other things this cell uses to fix its own genome, because we’re likely to find many more tools that we have no idea how they work or how they might be useful.”
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“When we think about cancer treatment today, we always think about treating cancer after it has occurred. What if we could prevent cancer from occurring in the first place?”
Watch this video where he explains it in easy-to-understand terms…
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