核DJ-1通过调节PARP1活动来调节DNA损伤的修复
Zhong-Xuan Wang1, Yi Liu1, Yao-Lin Li1
1Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
International journal of molecular sciences
|May 27, 2023
概括
帕金森病蛋白DJ-1对于修复DNA双链断裂 (DSB) 至关重要. 缺陷的DJ-1损害了DNA修复,可能导致帕金森病的发病.
科学领域:
- 分子生物学分子生物学
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
背景情况:
- DNA损伤和DNA修复受损与帕金森病 (PD) 病原发生有关.
- 连接这些过程的精确分子机制在很大程度上是未知的.
研究的目的:
- 研究帕金森病相关蛋白DJ-1在DNA双链断裂 (DSB) 修复中的作用.
- 阐明DJ-1影响DNA修复途径的分子机制.
主要方法:
- 描述DJ-1作为DNA损伤反应 (DDR) 蛋白质的特征.
- 对DJ-1在DNA损伤部位的招募进行分析.
- 研究DJ-1与PARP1.1的相互作用.
- 在具有DJ-1突变的细胞中评估DSB修复.
主要成果:
- DJ-1被招募到DNA损伤部位,并通过同源重组和非同源末端连接促进DSB修复.
- DJ-1 直接与 PARP1.1 的酶活性相互作用并刺激它.
- 患有DJ-1突变的PD患者细胞表现出缺陷的PARP1活性和受损的DSB修复.
结论:
- 核DJ-1在DNA修复和维持基因组稳定性方面发挥着关键作用.
- 由于DJ-1突变导致的缺陷DNA修复可能会导致帕金森病的发展.
相关概念视频
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
Nucleotide Excision Repair
3.6K
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...
3.6K
Long-patch Base Excision Repair
7.1K
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:
7.1K
Overview of DNA Repair
31.2K
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
31.2K
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
Negative Regulator Molecules
35.5K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.5K


