在激光诱导的DNA损伤部位的FUS蛋白的细胞类型依赖的招募动力学
Yu Niu1, Arun Pal1,2, Barbara Szewczyk3
1Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany.
International journal of molecular sciences
|March 28, 2024
概括
在DNA损伤部位的化在肉瘤 (FUS) 蛋白质动力学因细胞类型而异,影响神经退行性疾病研究. 了解FUS招募是研究DNA修复和细胞脆弱性的关键.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
背景情况:
- 积累的DNA损伤与衰老和神经退行性疾病有关.
- 化在肉瘤 (FUS) 蛋白质参与DNA修复途径,其突变导致肌缩性侧面硬化症 (ALS).
- 与ALS相关的FUS突变损害了DNA损伤的修复,这表明细胞类型特定的脆弱性.
研究的目的:
- 为了调查FUS蛋白对DNA损伤部位的招募动态是否在各种人体细胞类型之间有所不同.
- 探索细胞类型在FUS介导的DNA损伤反应和修复中的作用.
主要方法:
- 生成的人类诱导多能干细胞 (hiPSCs),表达野生型FUS与eGFP融合.
- 利用激光微辐射诱导局部DNA损伤.
- 开发了一种工作流程,以分析不同细胞衍生物中的DNA损伤部位的实时FUS招募动态.
主要成果:
- 在大多数研究的细胞类型中观察到FUS-eGFP对DNA损伤部位的招募.
- 人类诱导多能干细胞 (hiPSCs) 显示FUS招募减少,只有70%的细胞表现出这种反应.
- 在激光诱导的DNA损伤后,FUS招募的动力学在不同细胞类型之间存在显著差异.
结论:
- 在DNA损伤反应和修复过程中,FUS蛋白表现出细胞类型依赖的招募行为.
- 开发的实时分析工作流是研究DNA损伤部位的蛋白质动态的一个有价值的工具.
- 这些发现有助于理解DNA修复和神经退化中细胞类型特定的机制.
相关概念视频
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
02:10Translesion DNA Polymerases
10.0K
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
10.0K
02:37DNA Damage can Stall the Cell Cycle
9.1K
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...
9.1K
01:38Nucleotide Excision Repair
3.5K
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...
3.5K