通过 (6-4) 光聚酶进行DNA修复的光诱导的形状变化和产品释放
Masato Kondoh1, Kenichi Hitomi, Junpei Yamamoto
1Department of Chemistry, Graduate School of Science, Kyoto University, Oiwake, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan.
Journal of the American Chemical Society
|January 29, 2011
概括
光聚酶蛋白经历光诱导的构造变化,这对于DNA修复至关重要. 快速扩散的变化表明从修复的DNA中快速解离,使全基因组的修复.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 摄影化学的使用.
背景情况:
- 加密染色体/光解酶蛋白具有结构和辅因子相似性,但具有不同的功能,包括昼夜钟调节和DNA修复.
- 了解这些蛋白质的分子机制和动力学是至关重要的,但仍然不太了解.
- 由于其与人类加密染色体的相似性以及其依赖光的DNA修复功能, (6-4) 光解酶作为模型系统.
研究的目的:
- 调查光依赖DNA修复过程中 (6-4) 光解酶的分子机制和结构动力学.
- 解读黄胺二核酸 (FAD) 辅因子在关键修复反应中的作用.
- 为了阐明蛋白质的构造变化和扩散动态,以应对UV诱导的DNA损伤.
主要方法:
- 时间分辨率测量激素形成,扩散和蛋白质构造变化.
- 使用了体外系统来研究单次紫外线诱导损伤的DNA上的全长 (6-4) 光解酶.
- 在蓝光激活时监控体积变化和扩散动态.
主要成果:
- (6-4) 光解酶在蓝光激活时表现出显著的体积变化,表明与FAD辅因子相距的形状变化.
- 只有当 (6-4) 光解酶和受损DNA都存在时,才观察到显著的扩散变化.
- 这种扩散变化,具有50微秒的时间常数,表明蛋白质从修复后的DNA中快速解离.
结论:
- 观察到的构造和扩散变化对于光解酶的DNA修复效率至关重要.
- 从修复后的DNA中快速解离,使光解酶能够在整个基因组中访问和修复病变.
- 这些发现提供了对由加密染色/光解酶家族进行DNA修复的动态分子机制的见解.
相关概念视频
Nucleotide Excision Repair
Overview
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...
Nucleotide Excision Repair
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Mutations
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
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TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
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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...


