Cheating DNA Death: How an Extremophile Repairs Shattered Chromosomes
Fifty years ago, scientists uncovered a microbe capable of withstanding radiation in canned meat that had been bombarded with gamma rays. Named Deinococcus radiodurans — or "strange berry that withstands radiation" — the microorganism can survive doses of radiation up to 500 times that which would kill a human. These doses shatter D. radiodurans's DNA — just as they would in a human — but the microbe can repair its broken DNA and spring back to life within hours, depending on the dose. Researchers in France have finally determined how the most durable of extremophiles manages this trick. "We have discovered the mechanism by which a clinically dead cell resurrects back to life," explains Miroslav Radman of INSERM, France's public biomedical research institution. "This extreme radiation resistance is but a by-product of its selection for resistance to desiccation."
It's taken microbiologists 50 years, but the details of how D. radiodurans accomplishes the feat of resurrection have finally been figured out. Well, almost all the details.
When any type of cell is exposed to enough toxic chemicals, oxidative damage, high levels of ionizing radiation, or dehydration, what kills the cell is the fragmentation of its DNA. Without intact DNA, a cell can't manufacture proteins required to sustain its life. What D. radiodurans seems uniquely capable of doing is putting all of its fragmented DNA back together, and in just the right order. Something that all the king's horses and all the king's men could not do for Humpty Dumpty.
It turns out there are two stages to this process. In the first stage, the short fragments of (single-stranded) DNA are gradually reassembled into longer and longer pieces, until they are complete again. This is possible at all only because of the unique structure of DNA — DNA segments will stick together only when they have precisely matching base sequences in common. The process is facilitated in bacterial DNA by an enzyme called DNA polymerase I. The enzyme is encoded by a gene known as polA, which is present in all prokaryotes. However, the DNA polymerase I found in D. radiodurans apparently performs its job much more efficiently than its analogue in other bacteria. This natural process is similar to the laboratory process known as polymerase chain reaction (PCR), which also uses a polymerase enzyme.
But it's the second stage that is really special in D. radiodurans, and which has just been elucidated in the latest research:
... single long strands of DNA do little to resurrect the microorganism until the second stage of the newly discovered process kicks in: the simple pairing discovered by Watson and Crick decades ago — adenine (A) bonds with thymine (T), and cytosine (C) bonds with guanine (G). By inserting a special version of the nucleotide thymine that only binds to single strands of DNA — known as 5-bromodeoxyuridine — the researchers could observe as the single strands bonded with complementary strands to form complete chromosomes. "Once the chromosome is functional, the synthesis of all cellular components starts, and the cellular life is back," Radman says.
Interesting questions remain unanswered. An obvious one is how this unique capability of D. radiodurans evolved. Of course, it's obvious that the capability is highly advantageous to the survival of any microbe that inhabits an extreme environment. But there are few, if any, environments on Earth that have the level of ionizing radiation in which D. radiodurans can survive. So there must have been some other extreme feature of the environment, like toxic chemicals or frequent dessication. But then, why don't many other kinds of bacteria have the same abilities as D. radiodurans? Perhaps something even stranger happened, and D. radiodurans evolved in an environment outside Earth, with much more radiation — like Mars — and later migrated to Earth on a meteorite.
Another important question is: what makes the form of DNA polymerase in D. radiodurans so special and efficient? Knowing this could be very useful, for instance if we wanted to endow other bacteria with the same kind of survivability in extreme environments. We might want to do that to create bacteria that could detoxify toxic wastes.
Eukaryotic cells (found in "higher" animals than bacteria) use a different type of DNA polymerase than what prokaryotes use, and they are much more complex in general than bacteria. But yet another interesting question is whether it is possible to endow eukaryotic cells with a more effective DNA repair capability.
Microbe probe -- announcement of earlier (2001) research on D. radiodurans
Radiation-resistant organism reveals its defense strategies -- announcement of earlier (2003) research on D. radiodurans
Deinococcus radiodurans -- History and summary of research on D. radiodurans
D. radiodurans -- links to more information on D. radiodurans
Tags: biology, microbiology, extremeophiles