Scientists have discovered a protein that can directly stop DNA damage. And what’s even better: A new study shows that it appears to be a plug-and-play protein and can theoretically be incorporated into any organism. This makes it a promising candidate for a cancer vaccine.
DNA damage response protein C (DdrC) was found in a resilient little bacterium called Deinococcus radiodurans. DdrC appears to be very effective at detecting DNA damage, stopping it, and alerting the cell to start the repair process.
Perhaps the best feature of DdrC, however, is that it is quite self-sufficient and performs its task without the help of other proteins.
It should be relatively easy to ddrC gene into almost any other organism to improve DNA repair systems, as researchers at Western University in Canada discovered when they inserted it into boring old Escherichia coli.
“To our great surprise, it actually made the bacterium over 40 times more resistant to damage from UV radiation,” says biochemist Robert Szabla, lead author of the new work.
“This appears to be a rare example where a protein is actually a machine in its own right.”
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Untreated DNA damage can lead to a range of diseases. For example, UV light can damage the DNA in your skin cells, increasing the risk of skin cancer. If we can prevent or even reverse this damage, we could save lives.
“The ability to rearrange, edit and manipulate DNA in specific ways is the holy grail of biotechnology,” says Szabla.
“What if you had a scanning system like DdrC that monitored your cells and immediately neutralized damage? This could form the basis of a potential cancer vaccine.”
D. radiodurans is an obvious place to look for such a tool. The bacterium can survive radiation doses thousands of times higher than those needed to kill a human cell.
It was found that there were long stretches of outside the International Space Station and can even survive in conditions comparable to those on the surface of Mars. It turns out that DdrC plays a key role in this resilience.
“If a human cell has more than two breaks in its entire genome of one billion base pairs, it cannot repair itself and dies,” says Szabla.
“But in the case of DdrC, this unique protein helps the cell repair hundreds of broken DNA fragments into a coherent genome.”
The researchers used the Canadian Light Source’s powerful X-ray beam to study DdrC’s 3D shape and figure out how its magic works.
They discovered that the protein scans the DNA, looking for injuries to one or both strands. If it finds a single-strand or double-strand break, it binds to it and looks for another break of the same type.
When it finds two single-strand breaks, DdrC binds to both and immobilizes them, thereby compacting the DNA segment. It does the same with pairs of double-strand breaks, wrapping the two loose ends together to form a circle – much like tying a loop in a shoelace.
These repairs not only prevent the damage from getting worse, but they also signal the cell’s DNA repair mechanisms to patch the breaks.
Improved DNA repair has many benefits. Adapting this mechanism could also have a positive impact on genetic engineering, helping us develop vaccines against cancer and climate change-resistant crops. And it may even lead to other new tools.
“DdrC is just one of hundreds of potentially useful proteins in this bacterium,” says Szabla.
“The next step is to go even deeper and find out what else this cell uses to repair its own genome. Because we’re sure to find many more tools that we have no idea how they work or what use they have until we study them more closely.”
The study was published in the journal Nucleic acid research.
