热引起的突变过程的生物化学复制
1Department of Biological Sciences, Ohio University, Athens, Ohio, United States of America.
PloS one
|September 17, 2024
概括
自发的5-甲基细胞素去胺导致癌症突变特征 1. 这项研究重建了这一过程,证实了CpG>TpG突变是由于5-甲基细胞素去胺而产生的.
科学领域:
- 分子生物学分子生物学
- 癌症基因组学 癌症基因组学
- DNA 修复机制的修复机制
背景情况:
- 将5-甲基细胞素非酶性去胺化为乙胺是DNA损伤的关键来源.
- 这一过程被认为是癌症突变特征1的主要原因,在许多癌症类型中普遍存在.
研究的目的:
- 通过实验复制和验证癌症突变特征1形成的拟议机制.
- 阐明5-甲基细胞氨酸脱胺在CpG位点产生特定C>T突变中的作用.
主要方法:
- 在实验室中使用合成DNA,5-甲基和纯化的酵母DNA聚合酶 (δ和 ζ) 进行DNA去胺和合成的复制.
- 通过高温化加速自发DNA损伤诱导.
- 使用下一代DNA测序来量化突变频率.
主要成果:
- 重建过程仅在CpG环境中产生C>T突变,模仿签名1.
- 证明了CpG>TpG突变是由5-甲基细胞素去氨基化引起的.
- 确定了额外的C>G突变,归因于酵母DNA聚合酶 ζ作用于受热损坏的瓜残留物.
结论:
- 证实了5-甲基细胞素的去胺化是癌症突变特征的CpG>TpG突变的病因来源.突变特征1.
- DNA聚合酶活性和模板损伤有助于观察到的突变格局,尽管对瓜宁的损伤没有导致特定聚合酶的突变.
相关概念视频
Homologous Recombination
50.3K
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...
50.3K
Mismatch Repair
4.8K
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...
4.8K
Overview of DNA Repair
30.9K
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...
30.9K
Protein Denaturation
4.0K
The function of proteins depends on their native three-dimensional structure, which is dictated by the amino acid sequence of the specific protein. Folding of the polypeptide chain takes place under specific conditions that energetically favor the folded conformation. In contrast, protein denaturation occurs spontaneously under unfavorable conditions that disrupt the integrity of the folded conformation. Thus, the chemical and physical environment of a protein, such as significant changes in pH...
4.0K
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
Conservative Site-specific Recombination and Phase Variation
5.9K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
5.9K


