MazEF Toxin-Antitoxin System-Mediated DNA Damage Stress Response in Deinococcus radiodurans.

MazEF Toxin-Antitoxin System-Mediated DNA Damage Stress Response in Deinococcus radiodurans.
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MazEF 毒素-抗毒素系统介导的耐辐射奇球菌 DNA 损伤应激反应

DOI:
10.3389/fgene.2021.632423
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发表时间:
2021
影响因子:
3.7
通讯作者:
Zhao Y
Zhao Y
中科院分区:
生物学3区
文献类型:
--
作者:
Dai J;Chen Z;Hou J;Wang Y;Guo M;Cao J;Wang L;Xu H;Tian B;Zhao Y

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耐辐射异常球菌对包括丝裂霉素C(MMC)在内的各种DNA损伤剂具有显著的抗性。在D. MazF-dr是一种内切核糖核酸酶,其切割特异性先前已被表征。在此,我们进一步研究了MazEF系统在D.耐辐射的D. MazF(MazF-dr)是耐辐射杜氏菌TA系统毒素的第一个结构。耐辐射的MazF-dr通过互锁环的存在介导形成二聚体。转录分析显示,野生型(WT)菌株中有650个下调基因,但MazEF突变株中没有,这些基因可能受MazEF-dr对MMC治疗的反应调节。这些基因中的一些涉及膜运输和金属离子运输。随后,与WT菌株相比,MazEF突变菌株表现出更低的MMC诱导的细胞内铁浓度,活性氧(ROS),和蛋白质羰基化水平。这些结果提供了MazEF介导的D.抗辐射蛋白可能是由DNA损伤应激时ROS积累增加引起的。
Deinococcus radiodurans shows marked resistance to various types of DNA-damaging agents, including mitomycin C (MMC). A type II toxin-antitoxin (TA) system that responds to DNA damage stress was identified in D. radiodurans, comprising the toxin MazF-dr and the antitoxin MazE-dr. The cleavage specificity of MazF-dr, an endoribonuclease, was previously characterized. Here, we further investigated the regulatory role of the MazEF system in the response to DNA damage stress in D. radiodurans. The crystal structure of D. radiodurans MazF (MazF-dr) was determined at a resolution of 1.3 Å and is the first structure of the toxin of the TA system of D. radiodurans. MazF-dr forms a dimer mediated by the presence of interlocked loops. Transcriptional analysis revealed 650 downregulated genes in the wild-type (WT) strain, but not in the mazEF mutant strain, which are potentially regulated by MazEF-dr in response to MMC treatment. Some of these genes are involved in membrane trafficking and metal ion transportation. Subsequently, compared with the WT strain, the mazEF mutant strain exhibited much lower MMC-induced intracellular iron concentrations, reactive oxygen species (ROS), and protein carbonylation levels. These results provide evidence that MazEF-mediated cell death in D. radiodurans might be caused by an increase in ROS accumulation upon DNA damage stress.
细菌程序性细胞死亡和细菌多细胞行为。
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