The Sub1 nuclear protein protects DNA from oxidative damage

Reactive oxygen species are a by-product of aerobic metabolism that can damage lipid, proteins, and nucleic acids. Oxidative damage to DNA is especially critical, because it can lead to cell death or mutagenesis. Previously we reported that the yeast sub1 deletion mutant is sensitive to hydrogen peroxide treatment and that the human SUB1 can complement the sensitivity of the yeast sub1 mutant. In this study, we find that Sub1 protects DNA from oxidative damage in vivo and in vitro. We demonstrate that transcription of SUB1 mRNA is induced by oxidative stress and that the sub1D mutant has an increased number of chromosomal DNA strand breaks after peroxide treatment. We further demonstrate that purified Sub1 protein can protect DNA from oxidative damage in vitro, using the metal ion catalyzed oxidation assay.