对核孔相关的SUMO-依赖性全方位化酶的DNA损伤的功能向
Shigeki Nagai1, Karine Dubrana, Monika Tsai-Pflugfelder
1Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Science (New York, N.Y.)
|October 25, 2008
概括
核组织影响基因组的稳定性. 损坏的DNA被招募到核毛孔进行修复,由SUMO依赖的酶通路涉及Slx5/Slx8和Nup84.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 核组织影响基因表达,但其在基因组稳定中的作用不太了解.
- Slx5/Slx8复合体是一个小的,依赖于Ubiquitin-like修饰剂 (SUMO) 的Ubiquitin酶,参与DNA修复.
- 核孔是核和细胞质之间的界面上的关键结构.
研究的目的:
- 研究核组织在维持基因组稳定中的作用.
- 探索核孔复合体和DNA修复因子之间的功能关系.
- 阐明在核外围管理DNA损伤的机制.
主要方法:
- 经皮质微阵列分析 (E-MAP) 以确定DNA修复因子之间的功能关系.
- 实时成像观察受损DNA的动态招募.
- 染色体免疫沉 (ChIP) 来确认DNA-蛋白相互作用.
- 生物化学测试以确认蛋白质复合体之间的物理相互作用.
主要成果:
- 在核孔子复合体和Slx5/Slx8 SUMO依赖的泛素酶之间确定了一种功能联系.
- 核孔综合体和Slx5/Slx8.8之间确实存在物理相互作用.
- 实时观察到受损DNA到核孔的稳定招募.
- 转移到核孔的DNA需要Nup84复合体和Mec1/Tel1激酶.
- 连接核外围的供体位点以依赖于Slx8和Nup84的方式增强自发基因转换.
结论:
- 核毛孔通过促进DNA修复,在基因组稳定性中发挥作用.
- DNA链断裂被引导到核孔,通过一种保留的SUMO-依赖的E3结合酶通路进行处理.
- Slx5/Slx8结合酶和Nup84复合体是这种核孔相关的DNA修复机制的关键组成部分.
相关概念视频
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
02:10Translesion DNA Polymerases
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
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...
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...
02:36DNA 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...