Martínez Lissett E, Gómez Gerardo, Ramírez Norma, Franco Bernardo, Robleto Eduardo A, Pedraza-Reyes Mario
Department of Biology, Division of Natural and Exact Sciences, University of Guanajuato, Guanajuato 36050, Mexico.
School of Life Sciences, University of Nevada, Las Vegas, NV 89557, USA.
Antioxidants (Basel). 2024 Mar 8;13(3):332. doi: 10.3390/antiox13030332.
The guanine oxidized (GO) system of , composed of the YtkD (MutT), MutM and MutY proteins, counteracts the cytotoxic and genotoxic effects of the oxidized nucleobase 8-OxoG. Here, we report that in growing cells, the genetic inactivation of GO system potentiated mutagenesis (HPM), and subsequent hyperresistance, contributes to the damaging effects of hydrogen peroxide (HO) (HPHR). The mechanism(s) that connect the accumulation of the mutagenic lesion 8-OxoG with the ability of to evolve and survive the noxious effects of oxidative stress were dissected. Genetic and biochemical evidence indicated that the synthesis of KatA was exacerbated, in a PerR-independent manner, and the transcriptional coupling repair factor, Mfd, contributed to HPHR and HPM of the ΔGO strain. Moreover, these phenotypes are associated with wider pleiotropic effects, as revealed by a global proteome analysis. The inactivation of the GO system results in the upregulated production of KatA, and it reprograms the synthesis of the proteins involved in distinct types of cellular stress; this has a direct impact on () cysteine catabolism, () the synthesis of iron-sulfur clusters, () the reorganization of cell wall architecture, () the activation of AhpC/AhpF-independent organic peroxide resistance, and () increased resistance to transcription-acting antibiotics. Therefore, to contend with the cytotoxic and genotoxic effects derived from the accumulation of 8-OxoG, activates the synthesis of proteins belonging to transcriptional regulons that respond to a wide, diverse range of cell stressors.
由YtkD（MutT）、MutM和MutY蛋白组成的鸟嘌呤氧化（GO）系统可抵消氧化核碱基8-氧代鸟嘌呤的细胞毒性和基因毒性作用。在此，我们报告在生长的细胞中，GO系统的基因失活增强了诱变作用（高频率诱变，HPM），随后的超抗性导致了过氧化氢（HO）的损伤作用（过氧化氢高抗性，HPHR）。我们剖析了将诱变损伤8-氧代鸟嘌呤的积累与细胞进化及在氧化应激有害影响下存活的能力联系起来的机制。遗传和生化证据表明，KatA的合成以不依赖PerR的方式加剧，转录偶联修复因子Mfd促成了ΔGO菌株的HPHR和HPM。此外，如全局蛋白质组分析所揭示的，这些表型与更广泛的多效性效应相关。GO系统的失活导致KatA产量上调，并重新编程参与不同类型细胞应激的蛋白质的合成；这对（）半胱氨酸分解代谢、（）铁硫簇的合成、（）细胞壁结构的重组、（）AhpC/AhpF非依赖性有机过氧化物抗性的激活以及（）对转录作用抗生素的抗性增加有直接影响。因此，为应对8-氧代鸟嘌呤积累产生的细胞毒性和基因毒性作用，细胞激活了属于转录调节子的蛋白质的合成，这些调节子对广泛多样的细胞应激源作出反应。
