DNA损伤阻断的 RNAPII 促进转录合的修复
Yuka Nakazawa1, Yuichiro Hara1, Yasuyoshi Oka1
1Department of Genetics, Research Institute of Environmental Medicine (RIeM), Nagoya University, Nagoya, Japan; Department of Human Genetics and Molecular Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Cell
|March 7, 2020
概括
在RPB1-K1268的RNAPII无处不在对于DNA修复和转录恢复至关重要. 这一过程通过解决停滞的RNA聚合酶II来防止过早衰老和神经退行.
科学领域:
- 分子生物学
- 遗传学
- 生物化学
背景情况:
- 转录合核酸切除修复 (TC-NER) 在RNA聚合酶II (RNAPIIo) 在DNA损伤时停滞.
- RNAPIIo在哺乳动物DNA损伤反应中的作用尚不清楚.
研究的目的:
- 阐明RNAPII在哺乳动物DNA修复和转录恢复中的功能.
- 确定特定的无处不在位点及其在TC-NER中的机制作用.
主要方法:
- 在RNAPII上确定DNA损伤诱导的泛位 (RPB1-K1268).
- 开发一个线程特异的ChIP-seq方法来绘制无处不在的地图.
- 产生和分析RPB1-K1268R敲击小鼠.
主要成果:
- RPB1-K1268无处不在调节转录恢复和DNA损伤的抵抗力.
- 在RPB1-K1268的ubiquitination促进了TFIIH复杂的关联与停滞的RNAPIIo,涉及UVSSA-K414的ubiquitination.
- RPB1-K1268无处不在对于DNA修复和解决转录瓶至关重要.
- RPB1-K1268R小鼠表现出过早的衰老和神经退行.
结论:
- RNAPII无处不在提供双重保护机制:激活TC-NER和处理停滞的RNAPIIo.
- 这种双重机制可以防止长时间的转录停止,并防止神经退行.
相关概念视频
02:36DNA Damage can Stall the Cell Cycle
9.9K
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...
9.9K
02:36DNA Damage Can Stall the Cell Cycle
3.0K
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...
3.0K
02:37Restarting Stalled Replication Forks
6.2K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
6.2K
01:38Nucleotide Excision Repair
4.8K
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...
4.8K
01:08Nucleotide Excision Repair
40.4K
Overview
40.4K
02:10Translesion DNA Polymerases
10.9K
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...
10.9K