PLoS ONE：耐辐射球菌基因修复机制新认识

2月13日的《公共科学图书馆·综合》（PLoS ONE）杂志刊登了中国科学院北京基因组研究所基因组科学及信息重点实验室胡松年研究员与浙江大学华跃进研究员共同指导完成的文章——A Novel OxyR Sensor and Regulator of Hydrogen Peroxide Stress with One Cysteine Residue in Deinococcus radiodurans。

耐辐射球菌(Deinococcus radiodurans)是迄今为止发现的对电离辐射、紫外线、过氧化氢等一些DNA损伤剂都具有极强抗性的微小球菌。公认的耐辐射球菌有3种DNA修复方式：碱基切除修复、核苷酸切除修复和重组修复。但DNA修复过程的启动机制和修复的分子机理却知之甚少。

在细菌中，OxyR是过氧化物受体和转录调节元件，它能感受活性氧的存在并诱导抗氧化系统的功能。当细胞感受到时，OxyR蛋白通过两个保守的半胱氨酸残基（C199和C208）的二硫键的形成而被激活，在耐辐射球菌中，发现了一个基因DrOxyR基因具有特殊的特征，即它只有一个保守的半胱氨酸。Dr0615的突变体对H2O2表现超敏感，但对电离辐射不甚敏感。定点突变和体内功能分析表明，DrOxyR蛋白的C210对感受H2O2是必须的，定量PCR和转录丰度分析表明，DrOxyR既是转录激活子也是转录抑制子，能调节Mn/Fe的平衡。本研究表明，OxyR家族基因可以分为两类：2-Cys类和1-Cys类. （来源：中科院北京基因组所）

（《公共科学图书馆·综合》（PLoS ONE），doi:10.1371/journal.pone.0001602，Huan Chen, Songnian Hu, Yuejin Hua）

生物谷推荐原始出处：

A Novel OxyR Sensor and Regulator of Hydrogen Peroxide Stress with One Cysteine Residue in Deinococcus radiodurans

Huan Chen1,2, Guangzhi Xu1, Ye Zhao1, Bing Tian1, Huiming Lu1, Xiaomin Yu3, Zhenjian Xu1, Nanjiao Ying1, Songnian Hu2,3*, Yuejin Hua1*

1 Key Laboratory of Chinese Ministry of Agriculture for Nuclear-Agricultural Sciences, Institute of Nuclear-Agricultural Sciences, Zhejiang University, China, 2 James D. Watson Institute of Genome Sciences, Zhejiang University, Hangzhou, China, 3 Key Laboratory of Genome Science and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China

Abstract

In bacteria, OxyR is a peroxide sensor and transcription regulator, which can sense the presence of reactive oxygen species and induce antioxidant system. When the cells are exposed to H2O2, OxyR protein is activated via the formation of a disulfide bond between the two conserved cysteine residues (C199 and C208). In Deinococcus radiodurans, a previously unreported special characteristic of DrOxyR (DR0615) is found with only one conserved cysteine. dr0615 gene mutant is hypersensitive to H2O2, but only a little to ionizing radiation. Site-directed mutagenesis and subsequent in vivo functional analyses revealed that the conserved cysteine (C210) is necessary for sensing H2O2, but its mutation did not alter the binding characteristics of OxyR on DNA. Under oxidant stress, DrOxyR is oxidized to sulfenic acid form, which can be reduced by reducing reagents. In addition, quantitative real-time PCR and global transcription profile results showed that OxyR is not only a transcriptional activator (e.g., katE, drb0125), but also a transcriptional repressor (e.g., dps, mntH). Because OxyR regulates Mn and Fe ion transporter genes, Mn/Fe ion ratio is changed in dr0615 mutant, suggesting that the genes involved in Mn/Fe ion homeostasis, and the genes involved in antioxidant mechanism are highly cooperative under extremely oxidant stress. In conclusion, these findings expand the OxyR family, which could be divided into two classes: typical 2-Cys OxyR and 1-Cys OxyR.

全文链接：

http://www.plosone.org/article/fetchArticle.action?articleURI=info:doi/10.1371/journal.pone.0001602