Charge conduction properties of a parallel-stranded DNA G-quadruplex: implications for chromosomal oxidative damage.
The charge-flow properties and concomitant guanine damage patterns of a number of intermolecular and wholly parallel-stranded DNA G-quadruplexes were investigated. The DNA constructs were structurally well-defined and consisted of the G-quadruplex sandwiched and stacked between two Watson-Crick base-paired duplexes. Such duplex-quadruplex-duplex constructs were designed to minimize torsional stress as well as steric crowding at the duplex-quadruplex junctions. When anthraquinone was used to induce charge flow within the constructs, it was found that the quadruplex served both as a sink and as a moderately good conductor of electron holes, relative to DNA duplexes. Most strikingly, the quadruplex suffered very little charge-flow generated oxidative damage relative to guanines in the duplex regions and, indeed, to guanines in antiparallel quadruplexes reported in prior studies. It is likely that these differences result from a combination of steric and electronic factors. A biological conclusion that may be drawn from these data is that if, as anticipated, G-quadruplex structures form in vivo at the telomeres and other loci in eukaryotic chromosomes, their ability to serve as protective sinks against chromosomal oxidative damage may depend on their specific character and topology. From a separate perspective, our results on the conduction properties of duplex-quadruplex-duplex DNA composites suggest the utility of G-quadruplexes as junction modules in the construction of DNA-based biosensors and nanocircuitry.
Huang
Yu Chuan
YC
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BritishColumbia V5A 1S6, Canada.
Cheng
Alan K H
AK
Yu
Hua-Zhong
HZ
Sen
Dipankar
D
D002851:Chromatography, High Pressure Liquid; D002875:Chromosomes; D004591:Electrophoresis, Polyacrylamide Gel; D054856:G-Quadruplexes; D018384:Oxidative Stress