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Related Concept Videos

The DNA Replication Fork01:02

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An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork.   Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication...
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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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The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
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In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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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.
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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.
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Related Experiment Video

Updated: Oct 1, 2025

Visualization of DNA Replication in the Vertebrate Model System DT40 using the DNA Fiber Technique
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DNA replication fork speed underlies cell fate changes and promotes reprogramming.

Tsunetoshi Nakatani1, Jiangwei Lin1, Fei Ji2,3

  • 1Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München, München, Germany.

Nature Genetics
|March 8, 2022
PubMed
Summary
This summary is machine-generated.

Early embryo totipotency is linked to slow DNA replication fork speed. This finding suggests that manipulating replication fork speed could enhance cell reprogramming and plasticity.

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Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method
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Last Updated: Oct 1, 2025

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Area of Science:

  • Developmental Biology
  • Cellular Reprogramming
  • Genomics

Background:

  • Totipotency is crucial for early embryogenesis but its molecular mechanisms are not well understood.
  • Pluripotent stem cells can be reprogrammed into totipotent-like states, but the process requires further characterization.

Purpose of the Study:

  • To investigate the molecular underpinnings of reprogramming pluripotent stem cells into totipotent-like 2-cell-like cells (2CLCs).
  • To explore the role of DNA replication dynamics in cellular plasticity and cell fate transitions.

Main Methods:

  • DNA fiber analysis to assess DNA replication fork speed in totipotent cells and 2CLCs.
  • Analysis of replication timing (RT) changes during 2CLC emergence.
  • Experimental manipulation of replication fork speed to induce 2CLCs.
  • Assessment of reprogramming efficiency using somatic cell nuclear transfer (SCNT).

Main Results:

  • Totipotent cells in early mouse embryos exhibit slow DNA replication fork speed.
  • 2-cell-like cells (2CLCs) recapitulate this slow replication fork speed.
  • Changes in replication timing occur before 2CLC emergence, potentially predisposing cells to reprogramming.
  • Experimentally slowing replication fork speed induces 2CLCs and improves SCNT efficiency in vivo.

Conclusions:

  • Replication fork speed is a key regulator of cellular plasticity and the transition to a totipotent-like state.
  • Remodeling of DNA replication features, including fork speed and timing, drives changes in cell fate and reprogramming efficiency.