Artificial DNA Copies Just Like theReal Thing

[kullatiro]

Researchers took images of natural
DNA with man-made pieces inserted,
to find how the body's DNA copy
machine works with both the natural
and artificial DNA building blocks.
Their findings are a step toward
creating partly synthetic living
organisms.

 The language of life is about to
expand its vocabulary. An
international team of researchers
discovered that the body's copying
machine for DNA works in the same
way for manmade, artificial building
blocks of DNA as it does for the
natural kind.
If scientists find artificial DNA building
blocks work well and are safe to use,
the extra building materials could
create DNA that codes for new
molecules that the body can't make
now. The artificial DNA could also
form the basis of a partly synthetic
organism.
The DNA code in living things is made
of four different molecules, called
bases, that are nicknamed A, T, C and
G. In a double row of DNA, the bases
always link up to each other in a
specific way, with A's matching with
T's and C's matching with G's. In
2008, a team of researchers created a
third, artificial pair of DNA molecules
made to match with each other,
named NaM and 5SICS. In this new
study, some of the same researchers
used a technique called X-ray
crystallography to take pictures of A, T,
C, G, NaM and 5SICS while they were
getting copied in a test tube.
DNA is an important bodily process
that happens often, so that cells can
pass their genetic information on to
new cells that are created all the time,
such as skin or blood cells that
develop to replace old, worn-out cells.
After NaM and 5SICS were made,
several other groups of researchers
found that a natural strand of DNA
with NaM and 5SICS added to it will
still copy itself nearly as well as all-
natural DNA. Scientists didn't know
why it worked so well. They worried
they had somehow "tricked" the
body's DNA copying machine, called
DNA polymerase, said Floyd
Romesberg, a chemist at the Scripps
Research Institute in La Jolla, Calif.
Romesberg was one of the principal
inventors of NaM and 5SICS and was
involved in this new study , published
online yesterday (June 3) in the
journal Nature Chemical Biology.
The natural base pairs A, C, G and T
have specific shapes and line up
neatly with each other along their
edges when they're inside a DNA
helix. Scientists believe their shape
and neat fit are important for DNA
polymerase to work properly. On the
other hand, NaM and 5SICS aren't
shaped anything like the natural
bases. They don't use the same
chemical bonds as natural bases do
and they don't line up edge-to-edge. [
Move Over, DNA, and Meet the More
Durable XNA
]
With their X-ray crystallography
images, Romesberg — along with
colleagues in nearby San Diego, Calif.,
and in Germany — found that while
NaM and 5SICS aren't lined up edge-
to-edge inside a strand of DNA, they
shift so they are in the correct
formation for copying when DNA
polymerase comes along. "The DNA
polymerase apparently induces this
unnatural base pair to form a
structure that's virtually
indistinguishable from that of a
natural base pair," said Denis
Malyshev, another Scripps Institute
chemist in the study. He and his
colleagues think that the chemical
bonds the artificial bases use are
flexible, so they can shift positions
easily.
They also found that when the
artificial bases slide inside the
polymerase, like a sheet of paper
placed inside a copying machine, the
polymerase undergoes the same
chemical interactions as it does when
it works with natural bases. They also
found the polymerase refuses to pair
an artificial base with a natural base,
which is similar to how polymerases
will only match A's to T's and C's to
G's.
In the future, artificial DNA building
blocks like NaM and 5SICS could
expand the well-known "A, C, G, T"
vocabulary of DNA, according to a
statement from the Scripps Institute.
Synthetic bases may work even if they
aren't shaped like natural bases, as
long as they have flexible chemical
bonds, the way NaM and 5SICS do.
Romesberg, Malyshev and their
colleagues are now working on
tweaking NaM and 5SICS so that
natural DNA strands with those
synthetic bases added will copy even
more efficiently, at a rate that's closer
to the rate found in all-natural DNA,
they wrote in their paper. Once they
accomplish that, they can start
building synthetic organisms from the
ground up. "If we can get this new
base pair to replicate with high
efficiency and fidelity in vivo [i.e., in a
living organism], we'll have a semi-
synthetic organism," Romesberg said.

http://www.livescience.com/20734-artificial-dna-copies-real.html