In the July 20 issue of the Proceedings of the National Academy of Sciences
(PNAS), the researchers report that electrical charge moves through the DNA
bases by creating temporary distortions in their structure as the strands
naturally flex. The work suggests that the charge transport process is much more
complicated than previously believed.
"It's not at all like a conductor or a wire," said Dr. Gary B. Schuster, lead
author of the paper and dean of Georgia Tech's College of Sciences. "We think
this answers the question of how charge transfers through DNA, at least in a
broad-brush way."
The new charge transport model, dubbed "phonon-assisted polaron-like hopping,"
could help scientists better understand the mechanisms by which DNA is damaged
and repaired. It could also lead to development of new diagnostic techniques
based on recognition of charge transfer characteristics, and could one day open
up applications for one-dimensional DNA "wires" able to assemble themselves into
tiny circuits for micromachines.
Schuster compares the charge transport mechanism to the movement of a "Slinky,"
a child's toy that consists of a large spring that compresses and expands.
"When you inject a charge into DNA, the DNA responds by changing its structure
to accommodate that charge," he explained. "That change in structure distributes
the charge over several of the base pairs in the DNA. That creates a local
distortion in the DNA. That local distortion, just like the compression in the
Slinky toy, can move in the DNA as the structure moves normally in stretching,
bending and rotating."
The distortion, known as a polaron, can carry the charge a distance of up to a
few hundred Angstroms. The charge transfer stops when it encounters a specific
pairing of the DNA structure known as a GG step -- the location where two
guanine bases exist side-by-side. The charge trapped at this location then
oxidizes the guanine, causing damage that can lead to genetic mutations.
An experiment conducted in Schuster's lab by Dr. Paul T. Henderson -- now a
post-doctoral student at Massachusetts Institute of Technology -- showed that
the charge moves rapidly through a duplex strand of DNA with an efficiency that
is independent of the base sequence.
Using a tether just four atoms long, Henderson first created a linkage between
an anthraquinone and a specific location on a 60-base DNA segment. He then
irradiated the anthraquinone wth ultraviolet light, causing it to inject a
radical cation (a positively-charged ion) into the duplex chain of DNA base
pairs. He measured the progress of the cation through the DNA by observing where
it damaged the strand at GG steps.
The structural-independence and efficiency of the transport process were
unexpected and could not be explained by existing theories of electron
transport. Schuster believes two "averaging" mechanisms inherent in the polaron
process tend to even out the speed of the charge transport. This new mechanism
is possible only because of the dynamic nature of the DNA structure.
This dynamic characteristic of the DNA also opens a broad range of additional
questions concerning how specific DNA structure can affect charge transport.
"Our quest right now is to try to understand how the structure of DNA affects
its charge transport," Schuster explained. "We have a suspicion that one or
another of DNA's many structural forms might be a better conductor than the
standard form that researchers have been looking at. DNA is a flexible
structure, and the different forms have different distance relationships between
the atoms of DNA. It's the interaction between these atoms that furthers the
charge transport."
Understanding how electrical charge moves through DNA could help researchers
understand and perhaps develop a technique for reversing the damage done by
oxidation. Natural biological processes repair much of the damage, but some
damaged sections aren't repaired fast enough to avoid further damage -- and
genetic mutations.
"It may be possible to intervene and accelerate the repair mechanism or inhibit
the damage through pharmaceuticals or procedures," Schuster said. "That would be
important for certain people who have diseases in which the mechanisms for
repairing DNA are inefficient."
Other applications could include new diagnostic techniques for spotting the DNA
of disease-causing organisms, or even mutated copies of DNA. Also possible would
be mesoscale micromachines that take advantage of DNA's self-assembly
capabilities and the enzymes available to control that assembly.
"The charge transport mechanism of DNA is being explored as a mechanism for the
development of new gene diagnostics," he explained. "If DNA can act as a
conductor, you would be able to develop diagnostic probes that would allow you
to detect DNA from a bacteria, or a certain mutation."
Looking far down the road, DNA offers advantages over the micromachining
processes now being used.
"DNA has the amazing ability to construct itself," Schuster noted. "Rather than
having to build a machine atom by atom, you can take advantage of the ability of
DNA to organize itself into complex structures. DNA comes in prefabricated parts
that fit together, and that offers a tremendous advantage."
Beyond the researchers already mentioned, the work included Denise Jones,
Gregory Hampikian and Youngzhi Kan, all of Georgia Tech. The research was
sponsored by the National Institutes of Health and the National Science
Foundation.
--------------------------------------------------------------------------------
RESEARCH NEWS & PUBLICATIONS OFFICE
Georgia Institute of Technology
430 Tenth Street, N.W., Suite N-116
Atlanta, Georgia 30318 USA
MEDIA RELATIONS CONTACTS:
John Toon (404-894-6986);
E-mail: john.toon@edi.gatech.edu; FAX: (404-894-1826) or
Jane Sanders (404-894-2214) (770-975-1395);
E-mail: jane.sanders@edi.gatech.edu; FAX: (404-894-6983).
TECHNICAL INFORMATION:
Gary Schuster (404-894-0202); E- mail: (gary.schuster@cos.gatech.edu).
NOTE: Copies of the paper are available to reporters from the PNAS news office,
(202-334-2138), or E-mail (pnasnews@nas.edu)
WRITER: John Toon
--Secretary, Williamsport Area Computer Club <http://www.sunlink.net/wacc>Member, Susquehanna Valley Amateur Astronomers<http://www.geocities.com/CapeCanaveral/Hangar/2999/svaa.html>Personal Home Page: http://woodstock.csrlink.net/~jshaffer