Hydrogen peroxide, a potent inducer of global genomic instability

Oxidative stress has been implicated in a variety of human diseases. One plausible mechanism is that reactive active species can induce DNA damages and jeopardize genome integrity. To explore how oxidative stress results in global genomic instability in cells, our current study examined the genomic alterations caused by H₂O₂ exposure at the whole genome level in yeast. Using SNP microarrays and genome sequencing, we mapped H₂O₂-induced genomic alterations in the yeast genome ranging from point mutations and mitotic recombination to chromosomal aneuploidy. Our results suggested most H₂O₂-induced mitotic recombination events were the result of DNA double-stand breaks generated by hydroxyl radicals. Moreover, the mutagenic effect of H₂O₂ was shown to be largely dependent on DNA polymerase ζ. Lastly, we showed that H₂O₂ exposure allows rapid phenotypic evolution in yeast strains. Our findings indicate DNA lesions resulting from H₂O₂ may be general factors that drive genome instability and phenotypic evolution in organisms.