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相关概念视频

The Replisome03:01

The Replisome

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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...
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Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

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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,...
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Homologous Recombination02:31

Homologous Recombination

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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...
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Disassembly of Intermediate Filaments01:35

Disassembly of Intermediate Filaments

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Intermediate filaments (IFs) do not undergo spontaneous disassembly. Enzymes, kinases, and phosphatases add and remove phosphates from specific sites to regulate their disassembly. The IF concentration in the cytoplasm also regulates the disassembly. If the concentration crosses a threshold, it activates the protein kinases in the vicinity, allowing the phosphorylation of IFs.
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
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Replicative Cell Senescence02:15

Replicative Cell Senescence

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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...
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Nucleosome Remodeling02:54

Nucleosome Remodeling

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Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
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相关实验视频

Updated: Jun 19, 2025

Author Spotlight: Investigating the Motion Dynamics of the Eukaryotic Replisome Components at the Single-Molecule Level
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在人体细胞中表征复杂体分解的特征.

Rebecca M Jones1, Joaquin Herrero Ruiz1,2, Shaun Scaramuzza1

  • 1Institute of Cancer and Genomic Sciences, Birmingham Centre for Genome Biology, University of Birmingham, Birmingham, UK.

iScience
|July 26, 2024
PubMed
概括

在人类细胞中,复制体卸载需要MCM7无处不在和p97/VCP分离酶,并有保存后备机制的证据. 由于复制应激诱导,抑制剂的使用有限.

关键词:
生物化学 生物化学细胞生物学 细胞生物学遗传学 遗传学 遗传学 是一个

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Visualization of Replisome Encounters with an Antigen Tagged Blocking Lesion
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Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging
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相关实验视频

Last Updated: Jun 19, 2025

Author Spotlight: Investigating the Motion Dynamics of the Eukaryotic Replisome Components at the Single-Molecule Level
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Visualization of Replisome Encounters with an Antigen Tagged Blocking Lesion
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Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging
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科学领域:

  • 分子生物学分子生物学
  • 细胞生物学 细胞生物学
  • 遗传学 是一个遗传学.

背景情况:

  • 在S阶段,DNA复制需要及时通过数千个复制体进行基因组复制.
  • 从染色质中释放复制体是DNA复制的一个关键的最后一步.
  • 复制终止和复制体分解的机制在模型生物中得到了很好的研究,但在人类体细胞中不太了解.

研究的目的:

  • 研究人类体细胞中复合体分解的分子机制和调节.
  • 确定参与MCM7无处不在和复杂体卸载的关键蛋白质和途径.
  • 探索复合体分解机制的保护,包括潜在的备份路径.

主要方法:

  • 利用人体体细胞系统来研究复杂体释放.
  • 研究了CUL2LRR1,p97/VCP和UBXN7在MCM7无处不在和复制体分解中的作用.
  • 评估了库林泛素酶抑制剂 (CULi) 和p97抑制剂 (p97i) 对复杂体卸载和复制应激的影响.

主要成果:

  • 证明CUL2驱动的MCM7无处不在和p97/VCP分离酶对于人类细胞中的复杂体卸载至关重要.
  • 提供了保存的"备份"线粒体复制体分解途径的证据.
  • 表明CULi和p97i抑制了复制体卸载,但也诱导了复制应激,限制了它们的特定治疗应用.

结论:

  • 人体体细胞中的复制体分解依赖于一个保留的无处不在-分离酶通路,涉及MCM7,CUL2LRR1,和p97/VCP.
  • 识别备份拆卸机制强调了基因组维护的稳定性.
  • 针对这种途径的小分子抑制剂具有双重效应,影响分解和诱导复制应激,因此需要对治疗开发进行仔细考虑.