端粒i-motifs和C-strands通过端粒酶抑制并行G-四重复延伸
Roberto El-Khoury1, Morgane Roman1, Hala Abou Assi1
1Department of Chemistry, McGill University, Montreal, Quebec H3A 0B8, Canada.
Nucleic acids research
|September 24, 2023
概括
端粒C-链和i-基因可以抑制人类端粒酶活性. 这些结构通过与DNA基质和新生产物结合来干扰端粒延伸,影响端粒维护.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生化学
背景情况:
- 端粒DNA序列对于染色体的稳定性至关重要.
- 富含C的端粒DNA可以在酸性pH下形成i-motif结构.
- 在人体端粒生物学中i-motifs的体内作用仍然不清楚.
研究的目的:
- 调查端粒C链和i基因对人类端粒酶功能的影响.
- 探索i-motifs和G-quadruplexes在端粒中的潜在同时存在的可能性.
- 阐明C-链和i-动机抑制端粒酶的机制.
主要方法:
- 使用2'-氨基酸替代物以稳定中性pH的i-motifs.
- 基于共振能量转移 (FRET) 的研究来分析DNA结构.
- 进行了端粒酶活性测定,以测量酶功能和过程性.
主要成果:
- 稳定的i-图案与平行G-四重复体在端粒末端共存.
- 非结构化的C-链和i-动机都抑制了端粒酶的活性和过程性.
- 确定了三种抑制机制:基质结合,新生产物结合和干扰端粒酶解.
结论:
- 端粒C-链和i-基因可以作为人类端粒酶的抑制剂.
- 这些结构可能在调节端粒维护方面发挥重要作用.
- 这些发现表明,端粒C链在端粒生物学中具有潜在的抑制作用.
相关概念视频
Telomeres and Telomerase
23.4K
In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
23.4K
Replication in Eukaryotes
13.9K
In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
13.9K
Replicative Cell Senescence
3.7K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.7K
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
DNA Topoisomerases
31.4K
Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
31.4K
Single-Strand DNA Binding Proteins
14.2K
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...
14.2K


