腺病毒基蛋白使Mre11-Rad50-NBS1DNA修复复合体失活
Travis H Stracker1, Christian T Carson, Matthew D Weitzman
1Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Nature
|July 19, 2002
概括
Mre11-Rad50-NBS1复合体对于修复DNA双链断裂至关重要. 腺病毒E4蛋白质使该复合体失活,防止病毒DNA结合体的形成,并促进细胞转化.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 遗传学 是一个遗传学.
背景情况:
- 在哺乳动物细胞中,Mre11-Rad50-NBS1 (MRN) 复合体对DNA修复和基因组稳定至关重要.
- 腺病毒感染可以导致在缺少E4 (E4) 早期区域的情况下形成大型,无法打包的DNA结合体.
研究的目的:
- 为了研究参与腺病毒DNA结合体形成的细胞蛋白.
- 了解腺病毒E4产品在感染期间如何使这些细胞蛋白失活.
主要方法:
- 研究了Mre11-Rad50-NBS1复合体在腺病毒DNA结合中的作用.
- 在野生型腺病毒感染期间分析了MRN复合体的局部和命运.
- 确定了负责MRN复合体失活的病毒性coproteins.
主要成果:
- 功能性的Mre11和NBS1蛋白质是腺病毒DNA结合的必要条件.
- 该MRN复合体形成的焦点与病毒复制中心相邻.
- 野生型腺病毒感染导致MRN复合体的重组和降解.
- 三种病毒瘤蛋白调解MRN复合体的失活,防止结合.
结论:
- 腺病毒利用病毒瘤蛋白来向和禁用宿主细胞的MRN复合体,这是基因组稳定的关键因素.
- 这种非激活机制防止病毒DNA结合体的形成,并可能导致腺病毒介导的"撞击逃跑"转化.
相关概念视频
01:08Nucleotide Excision Repair
Overview
01:08Nucleotide Excision Repair
Overview
02:36DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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...
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...
02:36DNA Damage Can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...