Regulation of DNA repair by S-nitrosylation.
Regulation of DNA repair by S-nitrosylation.
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DOI：
10.1016/j.bbagen.2011.04.014
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发表时间：
2012-06
影响因子：
3
通讯作者：
Liu, Limin
中科院分区：
文献类型：
--
作者：
Tang, Chi-Hui;Wei, Wei;Liu, Limin
诱导型一氧化氮合酶（iNOS）的表达通常在炎症中被诱导，炎症是癌症的重要危险因素。一氧化氮（NO）及其相关活性氮可直接引起DNA损伤，增加DNA突变。他们也可以间接影响DNA突变的DNA修复蛋白的调制，特别是通过蛋白质S-亚硝基化，NO的一个关键的调节机制。在这里，我们回顾蛋白质的目标，分子机制，和潜在的作用NO在调节DNA修复，重点是S-亚硝基化的DNA修复蛋白的内源性NO合酶活性。最近的研究已经确定了一些关键的DNA修复蛋白作为S-亚硝基化的靶点，包括O 6-烷基鸟嘌呤-DNA-烷基转移酶（AGT），8-氧代鸟嘌呤糖基化酶，脱嘌呤-脱嘧啶核酸内切酶1和DNA依赖性蛋白激酶催化亚基。已显示S-亚硝基化调节DNA修复蛋白的活性、稳定性和细胞定位。蛋白质S-亚硝基化的水平取决于NO还原酶的NO合成和主要脱亚硝基酶S-亚硝基谷胱甘肽还原酶（GSNOR）的脱亚硝基化。由于GSNOR缺乏导致AGT的S-亚硝基化失调使AGT依赖的DNA修复失活，并且似乎对肝癌的发生起关键作用。对DNA修复蛋白S-亚硝基化的研究已经开始揭示炎症致突变和致癌作用的分子机制。调节蛋白质S-亚硝基化以影响DNA修复蛋白的活性可以提供一种治疗策略，以防止经常与慢性炎症相关的DNA损伤和突变，并使癌细胞对DNA损伤药物敏感。
Expression of the inducible nitric oxide synthase (iNOS) is commonly induced in inflammation, an important risk factor of cancer. Nitric oxide (NO) and related reactive nitrogen species can directly cause DNA damage to increase DNA mutation. They can also indirectly affect DNA mutation by modulation of DNA repair proteins, in particular through protein S-nitrosylation, a key regulatory mechanism of NO. Here we review protein targets, molecular mechanisms, and potential roles of NO in the regulation of DNA repair, with a focus on S-nitrosylation of DNA repair proteins by endogenous NO synthase activity. Recent studies have identified a number of key DNA repair proteins as targets of S-nitrosylation, including O6-alkylguanine-DNA-alkyltransferase (AGT), 8-oxoguanine glycosylase, apurinic-apyrimidinic endonuclease 1, and DNA-dependent protein kinase catalytic subunit. S-nitrosylation has been shown to modulate the activity, stability, and cellular localization of DNA repair proteins. The level of protein S-nitrosylation depends both on NO synthesis by NO synthases and on denitrosylation by a major denitrosylase, S-nitrosoglutathione reductase (GSNOR). Dysregulated S-nitrosylation of AGT due to GSNOR deficiency inactivates AGT-dependent DNA repair and appears to contribute critically to hepatocarcinogenesis. Studies on the S-nitrosylation of DNA repair proteins have started to reveal molecular mechanisms for the contribution of inflammation to mutagenesis and carcinogenesis. The modulation of protein S-nitrosylation to affect the activity of DNA repair proteins may provide a therapeutic strategy to prevent DNA damage and mutation frequently associated with chronic inflammation and to sensitize cancer cells to DNA-damaging drugs.
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影响因子：
2.7
作者：
Glassner, BJ;Weeda, G;Samson, LD
通讯作者：
Samson, LD
影响因子：
13.6
作者：
Foster MW;Hess DT;Stamler JS
通讯作者：
Stamler JS
DOI：
10.1056/nejmoa0804525
发表时间：
2008-11-06
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hoshida Y;Villanueva A;Kobayashi M;Peix J;Chiang DY;Camargo A;Gupta S;Moore J;Wrobel MJ;Lerner J;Reich M;Chan JA;Glickman JN;Ikeda K;Hashimoto M;Watanabe G;Daidone MG;Roayaie S;Schwartz M;Thung S;Salvesen HB;Gabriel S;Mazzaferro V;Bruix J;Friedman SL;Kumada H;Llovet JM;Golub TR
通讯作者：
Golub TR
影响因子：
16
作者：
Ciccia A;Elledge SJ
通讯作者：
Elledge SJ
影响因子：
7.4
作者：
Chien, YH;Bau, DT;Jan, KY
通讯作者：
Jan, KY