人类端粒C链填充模型由CST-Polα-primase进行填充
1Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
Trends in biochemical sciences
|August 16, 2023
概括
对于基因组完整性至关重要的端粒C链填充机制,通过对CTC1-STN1-TEN1 (CST) 和DNA聚合酶α-原酶 (polα-原酶) 之间的协调的新见解得到了澄清. 低温-EM结构揭示了这些复合体如何在突起处合成端粒C链.
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 生物化学
背景情况:
- 端粒维护对于真核生物的基因组完整性至关重要.
- 端粒合成涉及G-超悬延由端粒酶和C-链填充由DNA聚合酶α-原酶 (polα-原酶).
- 与端粒酶活性相比,C链填充机制的理解仍然较少.
研究的目的:
- 为了阐明端粒C链填充的机制.
- 详细介绍CTC1-STN1-TEN1 (CST) 复合体和多α-原酶之间的协调.
- 根据最近的发现,提出人类端粒C链填充模型.
主要方法:
- 关于端粒C链合成的最近研究的综述.
- 分析冷电子显微镜 (cryo-EM) 结构的CST-polα-原酶复合体.
- 整合结构数据与有关端粒维护的现有知识.
主要成果:
- 对C-链合成中CST和聚α-原酶之间的协调有新的见解.
- 低温电磁结构揭示了端粒模板的复杂组合.
- 通过复合体对端粒C链的新生合成的证明.
结论:
- 提出了人类端粒C链填充的综合模型.
- 这些发现增强了对基本基因组维护途径的理解.
- 这项研究强调了CST和聚α-原酶在端粒生物学中的关键作用.
更多相关视频
10:32Detection of Post-Replicative Gaps Accumulation and Repair in Human Cells Using the DNA Fiber Assay
Published on: February 3, 2022
6.3K
08:53Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method
Published on: May 2, 2025
418
相关概念视频
Telomeres and Telomerase
23.5K
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...
23.5K
Translesion DNA Polymerases
10.0K
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
10.0K
Homologous Recombination
50.7K
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...
50.7K
Replication in Eukaryotes
170.9K
Overview
170.9K
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
The Replisome
33.7K
DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...
33.7K
