Yu Lijian, Ma Hong, Ji Xincai, Volkert Michael R
Microbiology and Physiological Systems, University of Massachusetts Medical School, 55 Lake Ave. North, Worcester, MA, 01655, USA.
The Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, MA, USA.
Mol Cell Biochem. 2016 Jan;412(1-2):165-71. doi: 10.1007/s11010-015-2621-x. Epub 2015 Dec 26.
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 sub1Δ 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.
活性氧是有氧代谢的副产物,可损害脂质、蛋白质和核酸。对DNA的氧化损伤尤为关键,因为它可导致细胞死亡或诱变。此前我们报道酵母sub1缺失突变体对过氧化氢处理敏感,且人SUB1可弥补酵母sub1突变体的敏感性。在本研究中,我们发现Sub1在体内和体外均可保护DNA免受氧化损伤。我们证明SUB1 mRNA的转录受氧化应激诱导,且sub1Δ突变体在过氧化物处理后染色体DNA链断裂数量增加。我们进一步证明,使用金属离子催化氧化试验,纯化的Sub1蛋白在体外可保护DNA免受氧化损伤。