Novel mechanisms for eliminating oxidatively damaged RNA

消除氧化损伤RNA的新机制

• 批准号: 24657006
• 负责人: SEKIGUCHI Mutsuo
• 金额: $ 2.66万
• 依托单位: Fukuoka Dental College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24657006/
• 关键词: RNA; 酸化; 遺伝子発現; タンパク質; 発現異常; 酸化グアニン; 酵素; ストレス

Reactive oxygen species are produced as side products of oxygen utilization and can lead to the oxidation of nucleic acids and their precursor nucleotides. Among the various oxidized bases, 8-oxo-7,8-dihydroguanine seems to be the most critical during the transfer of genetic information because it can pair with both cytosine and adenine. During the de novo synthesis of guanine nucleotides, guanylate kinase hardly acts on an oxidized form of GMP (8-oxo-GMP) formed by the oxidation of GMP or by the cleavage of 8-oxo-GDP and 8-oxo-GTP by MutT protein. The 8-oxo-GTP produced in this way and by the oxidation of GTP can be used for RNA synthesis. This misincorporation is prevented by MutT protein, which has the potential to cleave 8-oxo-GTP as well as 8-oxo-GDP to 8-oxo-GMP. When (14)C-labeled 8-oxo-GTP was applied to CaCl2-permeabilized cells of a mutT(-) mutant strain, it could be incorporated into RNA at 4% of the rate for GTP.

活性氧物质作为氧利用的副产物产生，并且可导致核酸及其前体核苷酸的氧化。在各种氧化碱基中，8-氧代-7，8-二氢鸟嘌呤在遗传信息传递过程中似乎是最关键的，因为它可以与胞嘧啶和腺嘌呤配对。在鸟嘌呤核苷酸的从头合成过程中，鸟苷酸激酶几乎不作用于由GMP氧化或MutT蛋白切割8-氧代-GDP和8-氧代-GTP形成的氧化形式GMP（8-氧代-GMP）。以这种方式和通过氧化GTP产生的8-氧代-GTP可用于RNA合成。MutT蛋白阻止了这种错误掺入，MutT蛋白具有将8-氧代-GTP以及8-氧代-GDP切割为8-氧代-GMP的潜力。当（14）C-标记的8-oxo-GTP作用于CaCl 2-透化的mutT（-）突变株细胞时，它可以以GTP的4%的速率掺入RNA中。

项目成果

HeLa細胞に導入したグアニンヌクレオチドの運命

鸟嘌呤核苷酸导入 HeLa 细胞的命运

• 发表时间: 2012
• 作者: 関口猛;早川浩;関口睦夫
• 通讯作者: 関口睦夫

The identification of novel gene, MAPO2, that is involved in the induction of apoptosis triggered by O6-methylguanine

鉴定参与O6-甲基鸟嘌呤诱导细胞凋亡的新基因MAPO2

• 发表时间: 2012
• 期刊: PLOS ONE
• 影响因子: 3.7
• 作者: Ryosuke Fujikane;Masauki Sanada;Mutsuo Sekiguchi;Masumi HIdaka
• 通讯作者: Masumi HIdaka

My Path toward DNA repair

我的 DNA 修复之路

• 发表时间: 2012
• 期刊: DNA Repair
• 影响因子: 3.8
• 作者: Wei Gan;Ben Nie;Fei Shi;Xin-Min Xu;Chan Qian;Yasumitsu Takagi;Hiroshi Hayakawa;Mutuo Sekiguchi;Jian-Ping Cai;Mutsuo Sekiguchi
• 通讯作者: Mutsuo Sekiguchi

酸素ストレス下の遺伝子発現機構

氧胁迫下基因表达机制

• 发表时间: 2013
• 作者: 井口八郎;伊東理世子;関口猛;関口睦夫
• 通讯作者: 関口睦夫

Molecular mechanisms for accurate gene expression under oxidative stress

氧化应激下基因精确表达的分子机制

• 发表时间: 2012
• 作者: 伊東理世子;井口八郎;関口猛;関口睦夫;M. Sekiguchi
• 通讯作者: M. Sekiguchi