DNA损伤触发了通过DNA-PK和GOLPH3的戈尔吉分散
Suzette E Farber-Katz1, Holly C Dippold1, Matthew D Buschman1
1Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0707, USA.
Cell
|February 4, 2014
概括
通过DNA-PK,GOLPH3和MYO18A,DNA损伤触发了戈尔吉分散. 这一途径影响细胞生存,GOLPH3的过度表达赋予了对破坏DNA的抗体的抵抗力.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 对DNA损伤的核反应具有很好的特征,调节DNA修复,转录和细胞循环.
- 对DNA损伤的细胞质反应在很大程度上仍未被探索.
研究的目的:
- 为了研究细胞质对DNA损伤的反应.
- 阐明DNA损伤诱导的戈尔吉重组背后的分子机制及其在细胞存活中的作用.
主要方法:
- 在DNA损伤诱导后调查了戈尔吉重组.
- 利用分子生物学技术识别了关键的蛋白质,包括DNA-PK,GOLPH3和MYO18A.
- 在各种实验条件下 (关键蛋白质的耗尽/过度表达) 评估DNA损伤后的细胞存活率.
主要成果:
- DNA 损伤诱导了整个细胞质的戏剧性戈尔吉分散.
- 这种分散取决于依赖DNA的蛋白激酶 (DNA-PK),GOLPH3,MYO18A和F-actin.
- DNA-PK酸化GOLPH3,增强其与MYO18A的相互作用,并对Golgi施加力.
- DNA-PK,GOLPH3或MYO18A的消耗会减少DNA损伤后的细胞存活率.
- 在癌症中常见的GOLPH3过度表达,赋予了对DNA损伤剂的耐药性.
结论:
- 在对DNA损伤的反应中发现了一种新的细胞质路径,涉及DNA-PK,GOLPH3和MYO18A.
- 这一途径对于调节DNA损伤后的细胞生存至关重要.
- 戈尔吉在DNA损伤反应中的作用对癌症治疗和理解疾病进展有影响.
相关概念视频
02:36DNA Damage can Stall the Cell Cycle
9.9K
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...
9.9K
02:36DNA Damage Can Stall the Cell Cycle
2.9K
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...
2.9K
02:31Homologous Recombination
61.9K
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...
61.9K
02:37Restarting Stalled Replication Forks
6.2K
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,...
6.2K
02:10Translesion DNA Polymerases
10.9K
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...
10.9K
01:38Nucleotide Excision Repair
4.8K
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...
4.8K