考凯恩综合征B蛋白选择性地与分子间DNA的G-四重复结构进行分解和相互作用
Denise Liano1,2, Souroprobho Chowdhury1,2, Marco Di Antonio1,2,3
1Chemistry Department, Imperial College London, Molecular Science Research Hub, 82 Wood Lane, London W12 0BZ, United Kingdom.
Journal of the American Chemical Society
|December 2, 2021
概括
可凯恩综合征B (CSB) 蛋白在rDNA中选择性地结合和解脱分子间G四重复. 这种相互作用对于维持细胞平衡至关重要,并可能影响过早衰老的表型.
科学领域:
- 分子生物学
- 遗传学
- 生物化学
背景情况:
- 富含关氨酸的DNA形成G四重复体 (G4s),可以是分子内或分子间的.
- 研究主要集中在分子内G4s,因为在基因组DNA中感知到分子间G4s的丰度较低.
研究的目的:
- 识别与分子间G四重复体相互作用的内源蛋白.
- 研究这种相互作用在细胞过程中的功能作用.
主要方法:
- 蛋白质结合测试以确定不同G4结构的亲和力.
- 用于评估蛋白质活性的G4分辨率测试.
- 在不同CSB水平的细胞系中进行免疫覆盖.
- 在核细胞中染色的G4特异性抗体 (BG4).
主要成果:
- 可凯恩综合征B (CSB) 蛋白在rDNA中表现出对分子间G4s的小分子亲和力,与分子内G4s的结合最小.
- CSB可以选择性地分离分子间G4而不是分子内G4.
- 细胞中CSB的枯竭导致细胞核中的G4染色变化,通过CSB表达恢复.
结论:
- CSB是第一个在rDNA中对分子间G4s具有高选择性的内源蛋白.
- 在rDNA中形成的分子间G4s作为CSB的基质.
- 在rDNA中的CSB-分子间G4相互作用可能与细胞平衡和衰老的表型有关.
相关概念视频
Single-Strand DNA Binding Proteins
15.5K
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
15.5K
Fixing Double-strand Breaks
13.1K
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
13.1K
Restarting Stalled Replication Forks
6.0K
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,...
6.0K
Homologous Recombination
55.5K
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...
55.5K
Cohesins
4.8K
Cohesin protein complexes are a molecular glue that holds two sister chromatids together. They play an important role both in mitosis and meiosis. In mitosis, all cohesin complexes present on the chromosomes are removed before the start of the anaphase stage.
Cohesin complexes in Meiotic Division
Meiosis involves two distinct rounds of chromosomal segregation and cell divisions— Meiosis I followed by Meiosis II – producing four daughter cells. Meiosis I includes the separation of...
Cohesin complexes in Meiotic Division
Meiosis involves two distinct rounds of chromosomal segregation and cell divisions— Meiosis I followed by Meiosis II – producing four daughter cells. Meiosis I includes the separation of...
4.8K
Protein Complexes with Interchangeable Parts
2.6K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.6K


