A biological network in Saccharomyces cerevisiae prevents the deleterious effects of endogenous oxidative DNA damage.
In this study, we used Saccharomyces cerevisiae to identify a biological network that prevents the deleterious effects of endogenous reactive oxygen species. The absence of Tsa1, a key peroxiredoxin, caused increased rates of mutations, chromosomal rearrangements, and recombination. Defects in recombinational DNA double strand break repair, Rad6-mediated postreplicative repair, and DNA damage and replication checkpoints caused growth defects or lethality in the absence of Tsa1. In addition, the mutator phenotypes caused by a tsa1 mutation were significantly aggravated by defects in Ogg1, mismatch repair, or checkpoints. These results indicate that increased endogenous oxidative stress has broad effects on genome stability and is highly sensitive to the functional state of DNA repair and checkpoints. These findings may provide insight in understanding the consequences of various pathophysiological processes in regard to genomic instability.
Huang
Meng-Er
ME
Ludwig Institute for Cancer Research, CMME 3058, 9500 Gilman Drive, La Jolla, California 92093, USA.
Kolodner
Richard D
RD
D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism; D004260:DNA Repair; D004261:DNA Replication; D005816:Genetic Complementation Test; D016681:Genome, Fungal; D005838:Genotype; D008957:Models, Genetic; D009154:Mutation; D018384:Oxidative Stress; D010544:Peroxidases / Q000378:metabolism; D010641:Phenotype; D017382:Reactive Oxygen Species; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D016615:Telomere / Q000648:ultrastructure; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism
D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D010544:Peroxidases; C496253:Tsa1 protein, S cerevisiae; C471606:RAD6 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D045647:DNA Glycosylases