光诱导的电荷分离和DNA自我修复取决于序列的方向性和堆叠模式
Corinna L Kufner1, Sarah Crucilla1,2, Dian Ding3,4
1Department of Astronomy, Harvard-Smithsonian Center for Astrophysics 60 Garden Street Cambridge MA 02138 USA corinna.kufner@cfa.harvard.edu.
Chemical science
|February 9, 2024
概括
由于有利的基堆叠,TTAG DNA 序列比 GATC 更有效地自我修复环丁金二次体 (CPD). 这种DNA修复机制依赖于形状,影响电子转移和光稳定性.
科学领域:
- 摄影化学的使用.
- DNA损伤和修复的过程
- 计算生物物理学的计算生物物理学
背景情况:
- 紫外线光的吸收诱导DNA中的电荷分离,这是DNA损伤的关键一步.
- 特定的DNA序列,如GATC,可以通过顺序电子转移,通过循环butan胺二元体 (CPDs) 自修.
- 这种自我修复的效率受到核基氧化还原潜力和依赖序列的堆叠的影响.
研究的目的:
- 将TTAG序列的CPD自我修复效率与之前研究的GATC序列进行比较.
- 阐明在自我修复量子产量的观察到差异背后的分子机制.
- 调查DNA构造和替代光解活路径在光诱导电子转移中对DNA修复的作用.
主要方法:
- 进行了紫外线照射实验,以测量CPD形成和自我修复产量.
- 用分子动力学 (MD) 模拟来建模DNA结构动力学.
- 量子力学/分子力学 (QM/MM) 计算用于分析电子状态和能量景观.
主要成果:
- 与GATC (0.44 ± 0.18%) 相比,TTAG序列表现出较高的CPD自我修复量子产量 (0.58 ± 0.23%) 和GATC (0.44 ± 0.18%).
- 达到有利于自我修复的光静止平衡,TTAG (40 ± 16%) 的百分比比高于GATC (33 ± 13%).
- 在TTAG中,关氨酸 (G) 和氨酸 (A) 之间的增强堆叠重叠降低了A− ̇G+ ̇电荷转移状态的能量,促进了修复.
结论:
- DNA 序列构造显著影响光诱导电子转移效率和 DNA 自修.
- 替代光放松通路与电子转移机制竞争,影响整体修复效率.
- 了解这些机制可以预测具有增强电子转移和光稳定性的DNA序列,这与早期地球光化学有关.
相关概念视频
02:31Homologous Recombination
50.5K
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
50.5K
02:25Overview of DNA Repair
31.0K
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...
31.0K
02:04Fixing Double-strand Breaks
12.6K
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
12.6K
01:31Proofreading
6.3K
Synthesis of new DNA molecules is carried out by the enzyme DNA polymerase, which adds nucleotides on the daughter strand complementary to the template DNA strand. DNA polymerase has a higher affinity to add the correct base and ensures fidelity during DNA replication. Furthermore, it exhibits proofreading activity during replication, using an exonuclease domain that cuts off incorrect nucleotides from the nascent DNA strand.
Errors During Replication are Corrected by the DNA Polymerase...
Errors During Replication are Corrected by the DNA Polymerase...
6.3K
01:03Single-Strand DNA Binding Proteins
14.1K
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
14.1K
02:05DNA as a Genetic Template
21.9K
Two structural features of the DNA molecule provide a basis for the mechanisms of heredity: the four nucleotide bases and its double-stranded nature. The Watson-Crick model of double-helical DNA structure, proposed in 1952, drew heavily upon the X-ray crystallography work of researchers Rosalind Franklin and Maurice Wilkins. Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine for their work in 1962. Franklin was, controversially, excluded from the prize for...
21.9K