DNA不匹配修复蛋白 MutS 结合到 G x T 不匹配的晶体结构
M H Lamers1, A Perrakis, J H Enzlin
1Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam.
Nature
|October 26, 2000
概括
大肠杆菌MutS结合G x TDNA不匹配的晶体结构揭示了它的修复机制. 这种结构为DNA不匹配修复蛋白如何起作用及其与癌症倾向的联系提供了洞察力.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 遗传学 是一个遗传学.
背景情况:
- DNA不匹配修复 (MMR) 对于在DNA复制过程中保持基因组完整性至关重要.
- 人们对MMR的精确分子机制,特别是对MutS蛋白的初始不匹配识别,仍然不完全理解.
- 人类MMR蛋白质的突变与遗传性癌症有关,例如遗传性非多性结直肠癌.
研究的目的:
- 阐明DNA不匹配识别的分子机制由MutS.
- 为了解MMR提供结构基础.
- 为了将结构发现与人类癌症倾向突变相关联.
主要方法:
- 埃舍里希亚大肠杆菌的X射线晶体学MutS与G x TDNA不匹配结合,分辨率为2.2 Å.
主要成果:
- 晶体结构显示,MutS是一种具有明显单体构造的异构体.
- 特定的不匹配识别由一个MutS单体执行,该单体结合ADP并与DNA小沟相互作用,导致DNA扭曲.
- 两种单体的非特异性DNA结合域在DNA周围形成了一个类似紧的结构,其中核酸结合点远离DNA.
结论:
- 这项研究提出了 MutS-DNA 不匹配识别的详细结构模型.
- 这些发现澄清了DNA不匹配修复途径的初始步骤.
- 该结构为理解癌症相关突变对人类MutS同类 (MSH2/MSH6) 的影响提供了一个框架.
相关概念视频
01:36Mismatch Repair
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01:08Nucleotide Excision Repair
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01:36Mismatch Repair
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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...
01:20Mismatch Repair
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...