RIKEN SPring-8 Center, Harima Institute, Kouto, Sayo-gun, Hyogo, Japan.
PLoS One. 2011 Apr 28;6(4):e19053. doi: 10.1371/journal.pone.0019053.
Oxidative stress generates harmful reactive oxygen species (ROS) that attack biomolecules including DNA. In living cells, there are several mechanisms for detoxifying ROS and repairing oxidatively-damaged DNA. In this study, transcriptomic analyses clarified that disruption of DNA repair genes mutS and mutL, or the anti-recombination gene mutS2, in Thermus thermophilus HB8, induces the biosynthesis pathway for vitamin B(1), which can serve as an ROS scavenger. In addition, disruption of mutS, mutL, or mutS2 resulted in an increased rate of oxidative stress-induced mutagenesis. Co-immunoprecipitation and pull-down experiments revealed previously-unknown interactions of MutS2 with MutS and MutL, indicating that these proteins cooperatively participate in the repair of oxidatively damaged DNA. These results suggested that bacterial cells sense the accumulation of oxidative DNA damage or absence of DNA repair activity, and signal the information to the transcriptional regulation machinery for an ROS-detoxifying system.
氧化应激会产生有害的活性氧（ROS），攻击包括 DNA 在内的生物分子。在活细胞中，有几种机制可以解毒 ROS 并修复氧化损伤的 DNA。在这项研究中，转录组分析表明，破坏嗜热栖热菌 HB8 中的 DNA 修复基因 mutS 和 mutL，或抗重组基因 mutS2，会诱导维生素 B(1)的生物合成途径，维生素 B(1)可以作为 ROS 清除剂。此外，破坏 mutS、mutL 或 mutS2 会导致氧化应激诱导突变的速率增加。共免疫沉淀和下拉实验揭示了 MutS2 与 MutS 和 MutL 之前未知的相互作用，表明这些蛋白质协同参与修复氧化损伤的 DNA。这些结果表明，细菌细胞感知氧化 DNA 损伤的积累或 DNA 修复活性的缺失，并将信息传递给转录调控机制，以启动 ROS 解毒系统。
