A research team from the Georgia Institute of Technology has proposed a new explanation for how electronic charge transfer occurs in strands of DNA.
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.
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