增强的ELL相分离对于有效的DNA损伤修复至关重要,以重启转录和细胞存活
Sujay Pal1,2, Prathama Talukdar1, Arijit Ghosh3
1Laboratory of Transcription Biology, Molecular Genetics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.
Molecular and cellular biology
|December 22, 2025
概括
EAF1增强了延长因子ELL的相分离,促进DNA修复和在基因毒性压力后的转录重启. 这种相互作用对于DNA损伤后的细胞生存至关重要.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 遗传学 是一个
背景情况:
- 哺乳动物细胞在基因毒性压力期间重新启动转录后DNA修复.
- 在DNA损伤后进行最佳转录重启的机制尚未得到充分理解.
研究的目的:
- 调查EAF1介导的延长因子ELL相分离在DNA修复和转录重启中的作用.
- 阐明ELL如何与DNA修复因子相互作用,以获得高效的DNA损伤反应.
主要方法:
- 在体外和体内分离ELL蛋白的试验.
- 在基因毒性应激时对ELL●EAF1凝结物质的分析.
- 评估EAF1淘汰或ELL突变细胞中的DNA修复效率,转录重启和细胞存活率.
主要成果:
- 在ELL蛋白中表现出固有的相分离,形成液体凝结物.
- EAF1 增强了 ELL 阶段分离,改变了凝结物材料的特性.
- 基因毒性压力诱导ATM介导的酸化,增加EAF1结合和增强ELL相分离.
- 增强的ELL相分离增加了与DNA-PKc和Ku复合物的相互作用,用于DNA修复和转录重启.
- EAF1敲除或非相互作用的ELL突变损害了DNA修复,转录重启和细胞存活.
结论:
- 通过EAF1介导的ELL增强相分离对于高效的DNA损伤修复和转录重启至关重要.
- ELL●EAF1复合体在细胞对基因毒性压力的反应中起着至关重要的作用.
- 准ELL●EAF1相互作用可能是改善DNA修复和细胞存活的策略.
相关概念视频
DNA 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
DNA 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
Homologous Recombination
62.4K
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...
62.4K
Restarting 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
Nucleotide Excision Repair
4.9K
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...
4.9K
Nucleotide Excision Repair
40.5K
Overview
40.5K


