一种前所未有的核酸捕获机制用于切除DNA损伤
Emily H Rubinson1, A S Prakasha Gowda, Thomas E Spratt
1Department of Biological Sciences and Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37232, USA.
Nature
|October 8, 2010
概括
细菌花AlkDDNA糖酶通过捕获独特的溶剂暴露方向的额外螺旋性病变来修复受损的DNA. 这种机制促进了细胞毒性N3-甲基基的去除,这对于基因组保护和癌症治疗的见解至关重要.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 基因糖酶对基因组的完整性至关重要,它可以去除受损的 purin 基.
- 这些酶在DNA修复途径中至关重要,但可以干扰癌症化疗法.
- 了解葡萄糖酶的特异性是改善治疗策略的关键.
研究的目的:
- 为了阐明Bacillus cereus AlkDDNA糖酶特异性的结构基础.
- 调查AlkD识别和处理化 purin 基的机制.
- 提供对DNA修复及其对癌症治疗的影响的结构性见解.
主要方法:
- 进行X射线晶体学以确定AlkD的结构与修饰DNA的复合体.
- 生物化学试验分析基翻转和催化活性.
- 对DNA-蛋白相互作用和酶机制的结构分析.
主要成果:
- 晶体结构显示AlkD以暴露于溶剂的方向捕获额外螺旋性病变.
- 这种独特的结合方式促进了N3和N7基的水解.
- AlkD利用HEAT重复扭曲DNA骨干,使得异常基对的检测可以在没有插曲的情况下进行.
结论:
- AlkD采用一种独特的DNA修复机制,与其他已知的糖系酶不同.
- 该酶的结构为基化氨酸的基切除修复提供了一个模型.
- 研究结果提供了关于在癌症化疗法中克服抵抗机制的见解.
相关概念视频
01:54Base 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...
01:54Base 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...
01:08Nucleotide Excision Repair
Overview
01:38Nucleotide 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...
01:08Nucleotide Excision Repair
Overview
02:31Homologous Recombination
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...