相关实验视频
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Detection of Protein Ubiquitination
Published on: August 19, 2009
通过UV-DDB-ubiquitin结合酶复合体介导的XPC蛋白的紫外线诱导的无处不在
Kaoru Sugasawa1, Yuki Okuda, Masafumi Saijo
1Cellular Physiology Laboratory, RIKEN Discovery Research Institute, Japan Science and Technology Agency, Wako, Saitama 351-0198, Japan. sugasawa@riken.jp
Cell
|May 11, 2005
概括
在DNA修复过程中,Xeroderma pigmentosum群C (XPC) 蛋白质复合物的ubiquitylation至关重要. 这一过程依赖于紫外线损伤的DNA结合蛋白 (UV-DDB),促进了用于核酸切割修复 (NER) 的紫外线诱导的DNA损伤的转移.
科学领域:
- 分子生物学分子生物学
- DNA 修复机制的修复机制
- 细胞对紫外线辐射的反应
背景情况:
- 色素群C (XPC) 复合体对于在核酸切割修复 (NER) 过程中识别基因组DNA损伤至关重要.
- 紫外线光损伤的DNA结合蛋白 (UV-DDB) 复合体参与识别NER诱导损伤,但其确切的作用和与XPC的关系尚不清楚.
研究的目的:
- 研究在DNA修复过程中XPC和UV-DDB之间的相互作用中无处不在的作用.
- 阐明XPC无处不在对DNA结合和病变识别的功能后果.
主要方法:
- 研究了哺乳动物细胞中XPC蛋白对紫外线辐射的影响.
- 通过生物化学测试,研究了XPC和UV-DDB之间的物理相互作用.
- 分析了聚聚化对XPC和UV-DDB的DNA结合特性的影响.
- 评估了对UV诱导光产品的无细胞NER无处不在的要求.
主要成果:
- 在紫外线照射后,XPC经历了可逆的无处不在,取决于功能性UV-DDB活性.
- XPC和UV-DDB在物理上相互作用,并通过UV-DDB相关的ubiquitin结合酶进行多双双化.
- 聚二化修改了XPC和UV-DDB的DNA结合特性.
- 当UV-DDB与病变结合时,在UV诱导的 (6-4) 光产品的无细胞NER中,ubiquitylation是至关重要的.
结论:
- 泛基化是NER通路中的关键调节机制.
- 这些发现表明,无处不在作用调解了紫外线损伤的DNA病变从UV-DDB转移到XPC.
- 这项研究阐明了UV-DDB,XPC和无处不在在处理UV诱导的DNA损伤中的相互作用.
相关概念视频
Nucleotide Excision Repair
Overview
Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
Regulated Protein Degradation
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
The Unfolded Protein Response
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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...

