On the Non-Uniform Distribution of Guanine in Introns of Human Genes: Possible Protection of Exons against Oxidation by Proximal Intron Poly-G Sequences

Abstract

Earlier studies of oligonucleotides have shown that the rate of oxidation of the 5‘-G in GGG sequences is faster than that of other nucleotides in other sequences. Recent studies have shown that nondissolved, 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, and 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.