酵母 Nat4 通过其 N-终端乙转移酶活性对 histone H4 进行调节 DNA 损伤检查点信号传递
Mamantia Constantinou1, Evelina Charidemou1, Izge Shanlitourk1
1Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus.
PLoS genetics
|October 2, 2024
概括
表观遗传酶N终端乙转移酶4 (Nat4) 对于酵母中的DNA损伤反应 (DDR) 是至关重要的. Nat4 Nat4 Nat4 Nat4 Nat4 Nat4 Nat4 Nat4 Nat4 Nat4 Nat4 Nat4 Nat4 Nat4 Nat4 Nat4 Nat4 Nat4 Nat4 Nat4 Nat4 Nat4 Nat4
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 细胞生物学 细胞生物学
背景情况:
- DNA损伤反应 (DDR) 对于保持基因组完整性至关重要.
- 表观遗传酶,包括基因素修饰剂,通过改变色素结构,在DDR中发挥关键作用.
- N-终端乙转移酶4 (Nat4) 是一种已知的表观遗传修饰剂,可以乙化H4和H2A基因组.
研究的目的:
- 研究Nat4在Saccharomyces cerevisiae中DNA损伤反应中的作用.
- 阐明Nat4影响DNA损伤信号和修复的分子机制.
主要方法:
- 酵母遗传学:比较野生型和被删除nat4的菌株.
- 检测DNA损伤敏感性测试.
- 染色体免疫沉以评估蛋白质招募到双链断裂.
- 西方涂抹用于检测基因组修饰和蛋白质酸化.
主要成果:
- 缺乏Nat4的酵母细胞对DNA损伤的敏感性增加,并积累更多的DNA断裂.
- Nat4在DNA损伤时被招募到双链断裂,其基因表达被上调.
- 纳4缺乏会影响H2AS129ph修饰的沉积和Rad9和Mec1激酶的招募到双链断裂.
- 在被删除nat4的细胞中,Rad53的Mec1依赖酸化减少,这表明检查点激活受损.
- 在DDR中Nat4的功能是由其N端乙转移酶活性介导的,该活性介于基因素H4.
结论:
- 希斯N终端乙转移酶Nat4是酵母中DNA损伤反应途径的新型组成部分.
- Nat4通过通过基因素H4乙化调节DNA损伤信号级联,有助于基因组完整性.
- 这项研究揭示了一种新的表观遗传机制,它与维持基因组稳定性有关.
相关概念视频
DNA 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
Histone Modification
13.1K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.1K
Covalently Linked Protein Regulators
6.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.8K
Spreading of Chromatin Modifications
8.2K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
8.2K
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
Nucleotide 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


