title: Phosphorothioate DNA as an antioxidant in bacteria.
abstract: Diverse bacteria contain DNA with sulfur incorporated stereo-specifically into their DNA backbone at specific sequences (phosphorothioation). We found that in vitro oxidation of phosphorothioate (PT) DNA by hydrogen peroxide (H(2)O(2)) or peracetic acid has two possible outcomes: DNA backbone cleavage or sulfur removal resulting in restoration of normal DNA backbone. The physiological relevance of this redox reaction was investigated by challenging PT DNA hosting Salmonella enterica cells using H(2)O(2). DNA phosphorothioation was found to correlate with increasing resistance to the growth inhibition by H(2)O(2). Resistance to H(2)O(2) was abolished when each of the three dnd genes, required for phosphorothioation, was inactivated. In vivo, PT DNA is more resistant to the double-strand break damage caused by H(2)O(2) than PT-free DNA. Furthermore, sulfur on the modified DNA was consumed and the DNA was converted to PT-free state when the bacteria were incubated with H(2)O(2). These findings are consistent with a hypothesis that phosphorothioation modification endows DNA with reducing chemical property, which protects the hosting bacteria against peroxide, explaining why this modification is maintained by diverse bacteria.
authors: State Key Laboratory of Microbial Metabolism and School of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200030, People's Republic of China.
authors: Xinqiang
authors: X
authors: Xie
authors: Jingdan
authors: J
authors: Liang
authors: Tianning
authors: T
authors: Pu
authors: Fei
authors: F
authors: Xu
authors: Fen
authors: F
authors: Yao
authors: Yan
authors: Y
authors: Yang
authors: Yi-Lei
authors: YL
authors: Zhao
authors: Delin
authors: D
authors: You
authors: Xiufen
authors: X
authors: Zhou
authors: Zixin
authors: Z
authors: Deng
authors: Zhijun
authors: Z
authors: Wang
mesh_terms: D000975:Antioxidants / Q000737:chemistry*; D053903:DNA Breaks, Double-Stranded; D053837:DNA Cleavage; D004269:DNA, Bacterial / Q000737:chemistry* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D010463:Peracetic Acid; D054735:Phosphorothioate Oligonucleotides / Q000737:chemistry; D019163:Reducing Agents / Q000737:chemistry; D019779:Salmonella enterica / Q000187:drug effects / Q000235:genetics; D013455:Sulfur / Q000737:chemistry; D013873:Thionucleotides / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004269:DNA, Bacterial; D016877:Oxidants; D054735:Phosphorothioate Oligonucleotides; D019163:Reducing Agents; D013873:Thionucleotides; D013455:Sulfur; D006861:Hydrogen Peroxide; D010463:Peracetic Acid