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A Fight about the Toughest Microbe on Earth |
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By Kate Ruder Posted:
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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 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.
“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 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 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.
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