在V(D) J重组中DNA序列选择性的分子机制
Walker Hoolehan1, Justin C Harris1, Karla K Rodgers1
1Department of Biochemistry and Molecular Biology, Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, United States.
ACS omega
|October 2, 2023
概括
适应性免疫依赖于各种抗原受体 (AgR). 由RAG1/2蛋白质催化的V(D) J重组通过组装AgR基因产生这种多样性,但其特异性和调节的精确机制仍在探索中.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 脊椎动物的适应性免疫取决于各种抗原受体 (AgRs).
- V(D) J重组,一种切入和粘贴的过程,通过组装基因段来产生AgR多样性.
- 重组激活基因 (RAG1/2) 催化了与重组信号序列 (RSS) 相邻的V(D) J重组.
研究的目的:
- 审查关于RAG1/2与RSS组装的当前知识.
- 为了探索DNA裂变所需的RAG1/2中的构造变化.
- 检查RSS序列如何影响V(D) J重组效率和特异性.
主要方法:
- 关于V(D) J重组机制的文献综述.
- 对RAG1/2蛋白与RSS的相互作用进行分析.
- 在V(D) J重组中检查染色质结构调制.
主要成果:
- 共识 RSS 已经保留了带有可变间隔器的 heptamer 和 nonamer 序列.
- 许多RSS偏离了共识,V(D) J重组特异性的机制尚不清楚.
- 染色体调节对于AgR多样性至关重要,并防止异于目标的重组.
结论:
- 了解RAG1/2-RSS相互作用和序列读取是V(D) J重组的关键.
- 控制RAG1/2组合和DNA裂变的机制影响了适应性免疫和基因组稳定性.
- 需要进行进一步的研究,以阐明确切的调节V(D) J重组特异性的分子机制.
相关概念视频
Conservative Site-specific Recombination and Phase Variation
6.0K
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...
6.0K
Homologous Recombination
50.6K
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...
50.6K
Crossing Over
4.5K
Crossing over is the exchange of genetic information between homologous chromosomes during prophase I of meiosis I. Genetic recombination gives rise to allelic diversity in the newly formed daughter cells. In humans, crossing over produces genetically distinct haploid egg and sperm cells that undergo fertilization to produce unique offspring. Before cell division starts, the germ cell’s chromosome(s) undergo duplication in the S phase of the cell cycle. As the cells enter prophase I,...
4.5K
Base-pairing and DNA Repair
64.8K
64.8K
Gene Conversion
9.8K
Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
9.8K
Exon Recombination
3.6K
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon...
Exon shuffling follows “splice frame rules.” Each exon...
3.6K


