Phosphorothioate DNA as an antioxidant in bacteria.

Phosphorothioate DNA as an antioxidant in bacteria.
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硫代磷酸酯 DNA 作为细菌中的抗氧化剂

DOI:
10.1093/nar/gks650
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发表时间:
2012-10
影响因子:
14.9
通讯作者:
Wang Z
Wang Z
中科院分区:
生物学2区
文献类型:
--
作者:
Xie X;Liang J;Pu T;Xu F;Yao F;Yang Y;Zhao YL;You D;Zhou X;Deng Z;Wang Z

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不同的细菌含有DNA,其中硫以特定序列立体特异性地掺入其DNA骨架中(硫代磷酸化)。我们发现,在体外氧化硫代磷酸酯(PT)DNA过氧化氢(H2O2)或过氧乙酸有两种可能的结果:DNA骨架断裂或硫去除导致恢复正常的DNA骨架。通过使用H2O2挑战PT DNA宿主肠道沙门氏菌细胞来研究这种氧化还原反应的生理相关性。发现DNA硫代磷酸化与增加对H2O2生长抑制的抗性相关。当三个dnd基因中的每一个都失活时,对H2O2的抗性被废除,这三个基因是硫代磷酸化所必需的。在体内,PT DNA比PT游离DNA更能抵抗H2O2引起的双链断裂损伤。此外,修饰的DNA上的硫被消耗,DNA转化为PT自由状态时,细菌与H2O2孵育。这些发现与硫代磷酸化修饰赋予DNA还原化学性质的假设一致,这保护宿主细菌免受过氧化物的侵害,解释了为什么这种修饰被不同的细菌所保持。
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 (H2O2) 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 H2O2. DNA phosphorothioation was found to correlate with increasing resistance to the growth inhibition by H2O2. Resistance to H2O2 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 H2O2 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 H2O2. 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.
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