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A Fight about the Toughest Microbe on Earth

By Kate Ruder

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Scientists disagree about how the microbe pictured here survives radiation.
There is a microbe that can withstand thousands of times more radiation than a person can and still survive. When zapped by gamma rays in the laboratory, its DNA breaks into hundreds of pieces, but the microbe miraculously puts the pieces back together and goes on living. It has been nicknamed Conan the Bacterium.

It is also called Deinococcus radiodurans and is at the center of a contentious debate among scientists about how it puts back together—or repairs—DNA. In the past year and a half, three starkly different views about how the microbe repairs DNA have been put forth by three passionate and often quarrelling scientists.

The microbe could be used to design better drugs or clean up the environment. Cancer cells are often resistant to radiation and understanding how Deinococcus radiodurans resists radiation could help design better drugs. The U.S. Department of Energy has spent roughly $6 million on the microbe, including the sequencing of its genome in 1999, with the hopes that it could someday clean up hazardous metals at radioactive waste sites from the Cold War Era.

The story of Deinococcus radiodurans goes back to 1957 when it was found in a can of ground meat that spoiled despite having been sterilized by radiation . Scientists were shocked. How could it withstand such damaging radiation?

In the past four decades scientists have been banging their heads against the wall trying to determine the answer to that very question. Things have become more contentious in the past few years because the genome sequence didn’t offer any clear-cut clues.

No “super gene” popped out of the DNA sequence that could give the microbe its radiation resistance. All organisms have genes and proteins that help them repair nicks and mistakes in DNA, and many of the proteins Deinococcus radiodurans has for DNA repair look similar to the proteins found in other organisms.

This very fact inspired Abraham Minsky of the Weizmann Institute of Science in Israel to go a different way. In 2003, he argued that the physical shape of the genome—not the genes themselves—helps Deinococcus radiodurans repair DNA.

He proposed that all DNA in the genome is packed into a donut-like structure. Minsky says that having all the broken DNA pieces in one place in the cell rather than spread throughout the cell helps Deinococcus radiodurans repair DNA. The key is that the ends of DNA are kept in close physical proximity to each other. Even though they’re broken, they’re easy to mend.

“It’s the tight organization that keeps the fragments of DNA close together and that’s why it’s relatively easy to repair,” says Minsky. He published his findings in Science in January 2003 and a review of these findings in the Journal of Bacteriology last month.

Minsky says that proteins could also play a role in how Deinococcus radiodurans successfully repairs its DNA, but the prerequisite is its donut-shaped genome. The structure is more important than anything else.

There are probably many little things that contribute to the overall survival of the organism. --John Battista
“This is the secret,” he says of the physical structure of the genome. “I think people thought they would these magic proteins, but we have a problem that cannot be solved mainly by proteins.”

Another expert in the field Michael Daly also thinks that proteins are not the answer, but he could not more strongly disagree with Minsky’s “donut genome” idea.

Instead, Daly says the secret is the high level of metal called manganese in the cells of Deinococcus radiodurans. Daly works at Uniformed Services University of the Health Sciences in Bethesda, Maryland.

The manganese counterbalances the harmful effects of oxidation that follow radiation. It is essentially a powerful antioxidant that scavenges for free radicals in the cell. He published these findings in Science last month.

Daly says this idea could apply to human cells, specifically cancer cells. If you could limit the level of manganese in cancer cells you might make them more sensitive to radiation therapy.

“Some scientists are so heavily invested in the idea that the secret to extreme resistance to radiation lies in some magic combination of genes,” says Daly. “They could be looking for this unusual collection of genes until the end of all days.”

John Battista of Louisiana State University in Baton Rouge, is betting that he won’t be searching for these genes until “the end of all days.” He suspects that Deinococcus radiodurans uses a combination of proteins to help repair DNA, and he already has a few leads.

Battista has used DNA microarrays to analyze which genes are turned on and off when it repairs its DNA. In a new study, he identified one of probably many proteins that Deinococcus radiodurans uses to repair its DNA. He calls it the “DNA damage responses A protein” or DdrA for short.

This protein is like a band-aid on a wound. After the microbe’s DNA breaks into pieces, the protein acts as a cap on the ends of the DNA strands to prevent further damage until it can fully repair its DNA.

“One of the reasons why Deinococcus radiodurans is resistant to radiation is that it has a way of preserving the genome,” says Battista. “The protein preserves the integrity of genomic info until it can be repaired.” Battista published his findings in PLoS Biology last month.

So who’s right—no one, someone, or perhaps, all three? Only time and more science will tell. All three agree that more discussion is how science moves forward. But they also acknowledge that they’ve never all been in the same room together and don’t seem eager to be anytime soon.

“There are probably many little things that contribute to the overall survival of the organism,” says Battista.

“It’s a mistake to try to say, with the limited amount of information that we have about all three ideas, that one is only reason it survives radiation,” he says.

Harris, D. et al. Preserving genome integrity: the DdrA protein of Deinococcus radiodurans RI. PLoS Biology 2, 1629-1639 (October 2004).
Daly, et al. Accumulation of Mn (II) in Deinococcus radiodurans facilitates gamma-radiation resistance. Published online in Science September 30, 2004.
Englander, J. et al. DNA Toroids: Framework for DNA repair in Deinococcus radiodurans and in germinating bacterial spores. Journal of Bacteriology 186, 5973-5977 (September 2004).
Levin-Zaidman, S. et al., Ringlike structure of the Deinococcus radiodurans genome: A key to radioresistance? Science 299, 254-256 (January 10, 2003).

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