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Nov.
7, 2007: A stray bullet rips through the command
center, blowing holes in vital equipment and damaging the
data archives. Repair teams spring into action. The damage
must be patched up quickly or the control systems could go
haywire. It's literally a matter of life or death, and a decision
must be made: try to fix the damage in place, or move the
broken parts to the repair shop.
 This
is a drama that unfolds every day in the microscopic world
inside the cells of astronauts. High-speed particles of space
radiation zip through an astronaut's body. Occasionally, one
of these particles will strike and break a strand of DNA.
Because DNA carries a cell's genetic information and directs
its behavior, broken DNA can make a cell grow out of control
and even lead to cancer.
Right:
An artist's concept of DNA battered by space radiation.
Fortunately,
cells have teams of repair enzymes that try to fix this damage.
Scientists have long thought that these enzymes always go
to the site of injury and fix the DNA damage in place. But
new
research by Francis Cucinotta, the Chief Scientist for
NASA's Space Radiation Program at the Johnson Space Center,
and his colleagues suggests that cells might sometimes move
broken DNA to special "repair shops" instead.
It's
a new and controversial idea, Cucinotta says. "Scientists
just didn't discuss this idea before. People assumed that
the repair just happened right there where the damage occurred."
And indeed, the research shows that some strands of DNA are
repaired on the spot. Others, however, are relocated.
What's
the difference? "I think it is the most damaged
DNA that gets relocated," says Cucinotta.
If
so, this relocation system might provide a way for scientists
to distinguish between minor repairs and major ones. While
cells can often fix minor DNA damage successfully, they sometimes
botch major repairs. That can make the cell even more prone
to becoming cancerous, so selectively blocking the relocated
repairs could force a severely damaged cell to self-destruct
rather than attempt to fix itself, thus keeping the astronaut
healthier overall. "It may be better to let some cells
die off that have been damaged," Cucinotta says.
To
simulate space radiation, a team led by Sylvain Costes of
the Lawrence Berkeley National Laboratory exposed human cells
grown in the lab to one of three radiation types: gamma rays,
X-rays, and high-energy iron nuclei generated in the particle
accelerator at NASA's Space Radiation Laboratory, a part of
the Brookhaven National Laboratory in Upton, New York.
Above:
The radiation beam line at the NASA Space Radiation Laboratory.
[Larger image]
These
iron nuclei closely resemble cosmic rays, the most dangerous
form of space radiation and the most difficult kind to protect
astronauts from. The experiments using iron nuclei provided
the clearest evidence that cells might be moving broken DNA
to repair centers. These high-speed particles blaze straight-line
paths through cells. So spots of damage caused by a single
iron nucleus should be along that straight path.
Yet that's not the pattern that Costes and his colleagues
found when they analyzed images of real cells taken 10 minutes
after the cells were irradiated. By attaching fluorescent
molecules to some of the repair enzymes, the scientists could
see green, glowing spots in the cells wherever DNA was being
fixed. Rather than staying along the line where the damage
occurred, these glowing spots seemed to congregate at other
places within the cells.
"Often,
we saw repairs happening near the boundary between the dense
area containing all the chromosomes and the surrounding, emptier
regions," Cucinotta explains.
 Right:
DNA repair sites mapped by Costes et al at the NASA
Space Radiation Lab. [More]
Cells
might move damaged portions here because it's easier, he suggests.
DNA repair involves dozens of different enzymes. Rather than
trying to gather all these enzymes at the damage site, it
might be more efficient for cells to keep all these enzymes
in discrete locations near the chromosomes and bring injured
DNA to them.
"It's
more likely to be an accurate repair that way," Cucinotta
says. The transport mechanism that cells would use to move
the DNA around remains unknown.
While
the idea of DNA repair shops is fairly new, it's not without
precedent. When bacteria duplicate their chromosomes, they
do so by passing the DNA through a place in the cell called
the origin of replication rather than sending the copy-machine
enzymes to wherever the DNA happens to be.
If
future research supports the repair-shop idea, the discovery
could help NASA cope with the health threat posed to astronauts
by radiation.
For
one, understanding this relocation and repair system would
let researchers improve computer programs they use to estimate
space radiation health risks. Also, better knowledge of cells'
repair mechanisms could potentially reveal new molecular targets
for drugs that would someday improve astronauts' tolerance
to radiation. And that would make the occasional bullet--or
cosmic ray--a bit less alarming.
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Author: Patrick L Barry | Production Editor:
Dr. Tony Phillips | Credit: Science@NASA
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