Evaluation of genome designs for oxidation resistance guanine minimization and scavenger guanine /

by Friedman, Keith Albert.

Earlier studies of oligonucleotides have shown that the rate of oxidation of GGG sequences is faster than that of other nucleotide sequences. Recent studies have shown that non-dissolved, double-stranded DNA is a one-dimensional conductor of holes or electrons. GGG and longer poly-G sequences could, therefore, act as sacrificially oxidizable sinks for holes injected remotely into the DNA strand by oxidizing agents. This could cathodically protect the most essential parts of genes, their protein-coding exons. The protection of exons would be optimal if GGG sequences were concentrated near the termini of introns, flanking exons. We find, indeed, that GGG sequences are nonuniformly distributed in introns, that they are much more frequent near 5' intron termini, which flank the 3' ends of exons. We conclude that introns contain sacrificially oxidizable GGG sequences that are optimally positioned both to absorb holes injected directly into exons, and to intercept holes that could diffuse to exons from introns, which are much larger targets for oxidizing agents.