前rRNA促进了TopBP1-介导的DNA双链断裂反应
Di Xin1,2,3,4, Xiaochen Gai1,3,4, Yidi Ma1,3,4
1School of Life Sciences, Westlake University, Hangzhou, Zhejiang, 310024, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|August 15, 2023
概括
顶级BP1 顶级BP1
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:
- 在对DNA损伤的反应中,TopBP1对ATR激活至关重要.
- 对TopBP1在DNA修复中的作用的精确分子机制尚未完全理解.
研究的目的:
- 阐明TopBP1在DNA损伤反应中的作用的分子机制.
- 在基因毒性压力期间调查TopBP1与其他细胞组件的关联.
主要方法:
- 采用了无偏的蛋白质亲和力净化和RNA测序.
- 免疫光显微镜被用于可视化DNA双链断裂 (DSB) 的同定位.
- 用RNA聚合酶I抑制来研究前核糖体RNA (前rRNA) 生物发生的影响.
主要成果:
- 发现TopBP1与前核糖体RNA (前rRNA) 相结合,并与DSBs同定位.
- 将TopBP1招募到DSB中取决于rRNA前生物发生.
- TopBP1的BRCT4-5域识别了前rRNA,在DSB中促进了液体-液体相分离 (LLPS).
- 抑制前rRNA合成损害了TopBP1介导的细胞周期检查点激活和同源重组修复.
结论:
- 前核糖体RNA (pre-rRNA) 是TopBP1依赖的DNA损伤反应途径的关键组成部分.
- TopBP1与前rRNA的相互作用,可能通过LLPS,对于其在DSB的招募和功能至关重要.
- 预-rRNA生物发生对于高效的DNA损伤信号传递和由TopBP1.1调解的修复至关重要.
相关概念视频
02:31Homologous Recombination
50.7K
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...
50.7K
02:37Restarting Stalled Replication Forks
5.8K
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,...
5.8K
02:02DNA Topoisomerases
31.4K
Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
31.4K
02:04Fixing Double-strand Breaks
12.7K
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
12.7K
01:02Long-patch Base Excision Repair
7.0K
Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
7.0K
02:37DNA Damage can Stall the Cell Cycle
9.2K
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...
9.2K