Guanosine Distribution and Oxidation Resistance in Eight Eukaryotic Genomes

Abstract

Reactive oxygen species that attack DNA are continuously generated in living cells. Both the guanosine (G) mole fraction and its distribution should affect the stability of genomes and their parts to oxidation. At a lesser G content, genomes should be more oxidation resistant or "ennobled". Oxidant scavenging by G's in nonessential parts of introns and intergenic domains should decrease G oxidation in the essential exons. To determine whether genomes are indeed ennobled and whether oxidant-scavenging domains exist in genomes, the relative rates of guanosine oxidation in average exons, introns, and intergenic domains were estimated. Comparison among genomes indicated that average exons are ennobled in the genomes of Caenorhabditis (worm), Arabidopsis (plant), Saccharomyces (yeast), Schizosaccharomyces (yeast), and Plasmodium (malaria parasite), and that average introns and intergenic domains are ennobled in these genomes and in the genome of Drosophila (fly). The exon oxidation rates estimated for these genomes were less than the rate for the hypothetical "standard" genome, with a 0.25 mole fraction of uniformly distributed G. For Plasmodium the rate was half of that estimated for the standard genome. Average exons were not ennobled in the human or fly genomes; their G distributions were comparable to that in the standard genome. Instead, their exons were situated between introns and intergenic domains that could protect them by oxidant scavenging, the G's of their introns and intergenic domains outnumbering those of their exons 50-fold in humans and 4-fold in flies. The G distribution in the Encephalitozoon (parasite) genome was not protective relative to that of the standard genome.

DNA-based biosensor for the electrocatalytic determination of antioxidant capacity in beverages

“…Oxidative lesions in DNA are the primary risk factor for gene mutations, which plays a key role in carcinogenesis and aging (Freidman and Heller, 2004). Reactive oxygen species (ROS) are continuously generated in living cells, such as, in the inner mitochondrial membrane, outer membrane, and in several metabolic pathways in mammalian cells, for instance, in the microsomal electron transport.…”

The sacrificial role of easily oxidizable sites in the protection of DNA from damage

“…Correspondingly, it is suspected that certain intracellular antioxidants help prevent damage to DNA in the first place (3,4). Of special significance to the work reported here is the suggestion that DNA itself contains sacrificial nucleobases sequences that protect sensitive regions of the genome from oxidative damage (5–7). This proposal is based on the finding that one-electron oxidation of DNA introduces a radical cation that may migrate long distances by hopping through the duplex before being trapped by reaction with water or O 2 at a relatively low oxidation potential ( E OX ) site to generate a lesion (8–12).…”

“…The experiments reported here were designed as an analysis of the idea that long-distance radical cation migration in DNA has been adopted by nature as a mechanism to protect sensitive genomic regions from oxidative damage (5–7). Transfer of a radical cation through intervening DNA to low oxidation potential sites (cathodic protection) could channel it away from regions where lesions may do damage.…”

“…It has been suggested that concentration of these reactive sites in non-critical regions of the DNA (e.g. introns or intergenic domains) will reduce the oxidative load on important genomic domains and consume a radical cation without the concomitant formation of a deleterious mutation (7). The general validity of this proposal relies on efficient migration of the radical cation to a remote trap through oligomers containing nucleobases of various sequences.…”

Radical-induced purine lesion formation is dependent on DNA helical topology

“…Given their potential role in acting as protective sinks against chromosomal oxidative damage [27][28][29], G-quadruplex architectures have been extensively examined for their charge conduction properties. In particular, adjacent guanines in G-quartets appear to be very effective nucleobases for excess electron transfer [30].…”