对DNA的氧化损伤:对电离化DNA添加水以对电离子的辅助
Robert N Barnett1, Angelo Bongiorno, Charles L Cleveland
1Schools of Physics and Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
Journal of the American Chemical Society
|August 17, 2006
概括
离子通过协助质子穿机制促进DNA氧化损伤,形成8-oxo-7,8-dihydroguanine (8-OxoG). 这种对DNA修复途径的对策效应对于理解突变发生和衰老至关重要.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 计算化学计算化学
背景情况:
- 氧化性DNA损伤,特别是8-oxo-7,8-dihydroguanine (8-OxoG) 的形成,与突变发生,衰老和癌症有关.
- 了解DNA损伤的机制对于开发治疗策略至关重要.
研究的目的:
- 阐明 counterions 在DNA 氧化损伤途径中的作用.
- 确定涉及8-OxoG形成的特定配置和反应途径.
主要方法:
- 利用分子动力学和B-DNA四分相机上的初始量子模拟.
- 研究的反应途径受当地对子体安排的影响.
主要成果:
- 确定了一个低激活屏障 (0.73 eV),用于主要槽中的Na(+) 离子促进的8-OxoG形成.
- 揭示了一种反辅助的质子穿机制,涉及水分子和离子.
- 观察到水和骨干酸盐组之间的结合复合物的形成.
结论:
- 对比的布置显著影响了氧化DNA损伤的激活能量和机制.
- 纳+辅助的质子穿机制为8-OxoG形成提供了详细的途径.
- 实验证据支持通过选择性酸盐修饰的拟议机制.
更多相关视频
12:15Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter
Published on: May 29, 2019
10:12Quantitative Detection of DNA-Protein Crosslinks and Their Post-Translational Modifications
Published on: April 21, 2023
相关概念视频
Nucleotide Excision Repair
Overview
Overview of DNA Repair
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
Nucleotide Excision Repair
Overview
Overview of DNA Repair
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
Nucleotide Excision Repair
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Spontaneous and Induced Mutations
Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).
