在基因毒性应激反应中分离相位的核糖体新生链复合体
Orsolya Németh-Szatmári1, Bence Nagy-Mikó1, Ádám Györkei2,3
1Department of Biochemistry and Molecular Biology, University of Szeged, 6726 Szeged, Hungary.
概括
组合体,核蛋白复合体,参与DNA修复. 这些在酵母和人体细胞中发现的结构,动态地对DNA损伤作出反应,这表明它们在细胞修复机制中的作用.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 组合体是EDTA和RNase耐药的核糖蛋白 (RNP) 复合体,由暂停的核糖体和新生的多链组成.
- 之前的研究在酵母和人类细胞中确定了与蛋白质酶子单元Rpt1相关的组合体,突出显示了无序的N终端新生链的作用.
研究的目的:
- 通过生物信息学和实验验证,识别一些相关RNP的新组合.
- 调查组合体在DNA修复途径中的作用及其对DNA损伤刺激的反应.
主要方法:
- 酵母蛋白复合体的生物信息分析,以预测N终端疾病的倾向.
- 使用酵母Sgs1 DNA酶和人类BLM酶进行实验验证.
- 组基因组相关RNAs的RNA测序.
- 传输电子显微镜用于可视化细胞结构.
主要成果:
- 生物信息学预测了DNA修复蛋白在潜在的组合体组件中进行丰富.
- 新生的Sgs1链形成组合体,SGS1mRNA在紫外线暴露时动态转移.
- 人类BLM螺旋酶在组合体中被确定,并为DNA修复蛋白的mRNA进行了丰富.
- 1,6-二醇破坏了组合类结构的组合,并增加了对X射线治疗的敏感性.
结论:
- 集合体与酵母和人体细胞中的DNA修复蛋白有关.
- 组合的动力学受到外部刺激的调节,特别是DNA损伤.
- 这些发现表明,聚合体在物种间的DNA损伤反应中起着重要作用.
相关概念视频
Stringent Response in E. coli
31
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
31
Other Stress Responses in Bacteria
33
Bacteria have global regulatory systems that control several types of stress mechanisms. These include Pho regulon and the heat shock response, which are essential systems for environmental adaptation, such as nutrient limitation and proteotoxic stress. The Pho regulon and the heat shock response exemplify bacterial resilience, enabling rapid adaptation to fluctuating environmental conditions.Pho RegulonBacteria require phosphorus for essential cellular processes, including nucleic acid...
33
Regulation of the Unfolded Protein Response
2.5K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K
Restarting 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
DNA 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
Bacterial Protein Maturation
36
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
36


