一个与DNA基质复合的胺二元切除修复酶的原子模型:受损DNA识别的结构基础
D G Vassylyev1, T Kashiwagi, Y Mikami
1Protein Engineering Research Institute, Japan.
Cell
|December 1, 1995
概括
结构分析了T4内核酶V,一种DNA修复酶. 它的复杂性与受损的DNA揭示了独特的扭曲结构和翻转的基底,解释了DNA修复机制.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- T4内核酶V是一种关键的DNA修复酶,参与了胺二聚体的去除.
- 基因切除修复是保持基因组完整性的关键途径.
- 了解DNA-蛋白相互作用对于理解DNA修复过程至关重要.
研究的目的:
- 确定与受损DNA复合的T4内核酶V的高分辨率晶体结构.
- 阐明T4内核酶V对胺二聚体的识别和结合的结构基础.
- 为了深入了解DNA修复的催化机制.
主要方法:
- 在2.75A分辨率的X射线晶体学.
- 在T4内核酶V和含有乙胺二聚体的合成DNA复合体之间形成复合体.
- 酶-DNA复合体的结构分析和可视化.
主要成果:
- 晶体结构揭示了一个急剧扭曲的DNA复合在胺二次位点 (60度的倾斜).
- 观察到一个互补的腺基被翻转出DNA螺旋.
- 这种翻转出来的基因被隔离在T4内核酶V蛋白内特定的腔内.
结论:
- 独特的DNA构造和基因翻转对于T4内核酶V识别受损DNA至关重要.
- 这些发现为了解酶的催化机制提供了结构基础.
- 这项研究表明,其他修复酶对DNA损伤的识别有一般机制.
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...
Base Excision Repair
One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
The first step of...
Nucleotide Excision Repair
Overview
Base Excision Repair
One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
The first step of...
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...


