在一个YBX1调节PARP1居住在DNA双链断裂的复合体中的非编码YRNA片段
Annabelle Shaw1, Kamal Ajit1, Manon Chataignier1
1Sir William Dunn School of Pathology, University of Oxford, South Parks Road, OxfordOX1 3RE, United Kingdom.
Nucleic acids research
|June 18, 2025
概括
带有YBX1-包装的ysRNA的损伤衍生外体赋予辐射保护. 这些小RNAs通过增强双链断裂部位的PARP1活性来促进DNA修复和细胞存活.
科学领域:
- 细胞生物学 细胞生物学
- 分子瘤学分子瘤学
- RNA生物学的RNA生物学
背景情况:
- DNA损伤反应 (DDR) 对于保持基因组完整性和预防癌症等疾病至关重要.
- DDR路径利用蛋白质和RNA组件进行细胞内和细胞间信号传递.
- 外体细胞调解细胞间的通信,可能会影响细胞对损伤的反应.
研究的目的:
- 为了研究损伤衍生的外体在细胞保护DNA损伤中的作用.
- 为了确定外体内负责辐射保护的特定分子组成部分.
- 阐明这些成分促进DNA修复的机制.
主要方法:
- 从受损细胞中对外体隔离和表征.
- RNA测序和小非编码RNAs (ysRNAs) 的识别.
- 生物化学试验用于研究蛋白质-RNA相互作用 (YBX1-ysRNA).
- 使用显微镜进行细胞局部化研究.
- 对DNA修复动力学和细胞存活试验的分析.
- 研究YBX1/ysRNA复合体与PARP1.1之间的相互作用.
主要成果:
- 来自损伤的外体赋予辐射保护.
- Y盒结合蛋白1 (YBX1) 包装的Y3衍生小乌克兰RNAs (ysRNAs) 是关键的媒介.
- ysRNAs被甲基化并与受体细胞中的YBX1结合.
- YBX1/ysRNA复合体局部化到双链断裂 (DSB) 位点.
- 这种复合物通过与PARP1.1形成复合物来促进DNA修复和细胞存活.
- YBX1促进了ysRNA的ADP-ribosylation,增强了PARP1的活性和在DSB中的居住时间.
结论:
- 含有YBX1-包装的ysRNA的损伤衍生外体是强大的辐射保护剂.
- ysRNAs是PARP1介导的ADP-ribosylation的新型基质.
- YBX1/ysRNA复合体在增强DNA双链断裂修复和促进细胞存活方面发挥着关键作用.
相关概念视频
Restarting Stalled Replication Forks
5.9K
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,...
5.9K
Homologous Recombination
52.8K
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...
52.8K
Long-patch Base Excision Repair
7.2K
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:
7.2K
DNA Damage can Stall the Cell Cycle
9.3K
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...
9.3K
Fixing Double-strand Breaks
12.9K
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...
12.9K
Base-pairing and DNA Repair
65.2K
65.2K


