甲基化调节紫外线诱导的DNA损伤反应
Yang Xiang1,2, Benoit Laurent1,2, Chih-Hung Hsu1,2
1Division of Newborn Medicine and Epigenetics Program, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
Nature
|March 16, 2017
概括
RNA甲基化 (m6A) 迅速标记DNA损伤部位,招募DNA聚合酶 κ以增强紫外线暴露后的修复和细胞存活.
科学领域:
- 分子生物学
- 表观遗传学
- DNA 修复
背景情况:
- 细胞的生存取决于对抗不断的损伤威胁的精确DNA维护.
- DNA损伤反应 (DDR) 系统检测,修复DNA损伤,并停止细胞分裂以完成修复.
研究的目的:
- 研究RNA甲基化,特别是N6-甲基氨酸 (m6A) 在DNA损伤反应中的作用.
- 阐明m6A影响DNA修复途径的机制,特别是对紫外线 (UV) 辐射的反应.
主要方法:
- 在紫外线照射后监测DNA损伤部位的RNA修饰动态.
- 评估甲基转移酶类3 (METTL3) 和脂肪质量和肥胖相关蛋白 (FTO) 对m6A水平和DNA修复的影响.
- 在METTL3活性存在或不存在的情况下,评估DNA聚合酶 κ (Pol κ) 对UV诱导的DNA损伤部位的招募.
- 分析METTL3损失对DNA修复和细胞紫外线敏感性的功能影响.
主要成果:
- 在紫外线照射后2分钟内,N6-甲基氨酸 (m6A) 在DNA损伤部位迅速和暂时诱导RNA修饰.
- METTL3作为甲基转移酶,而FTO作为脱甲基酶,调节m6A水平以应对DNA损伤.
- 导致METTL3催化活性丧失,导致紫外线诱导的循环胺添加物的修复延迟,并增加紫外线敏感性.
- METTL3对于快速招募DNA聚合酶 κ (Pol κ) 到UV诱导的DNA损伤部位至关重要.
结论:
- 在紫外线引起的DNA损伤反应中,一种修饰起着新的关键作用.
- 一个RNA作为一个信号机制来招募特定的DNA修复蛋白,如Pol κ,到损伤部位.
- 这种m6A介导的招募促进了高效的DNA修复,并提高了紫外线暴露后的细胞存活率.
相关概念视频
01:38Nucleotide Excision Repair
5.4K
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...
5.4K
01:08Nucleotide Excision Repair
41.4K
Overview
41.4K
01:35Mutations
44.9K
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
44.9K
01:39Mutations
95.3K
Overview
95.3K
01:20Mismatch Repair
6.8K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
6.8K
01:36Mismatch Repair
44.3K
Overview
44.3K