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Related Concept Videos

The DNA Replication Fork01:02

The DNA Replication Fork

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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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Replication in Prokaryotes01:32

Replication in Prokaryotes

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DNA replication has three main steps: initiation, elongation, and termination. Replication in prokaryotes begins when initiator proteins bind to the single origin of replication (ori) on the cell's circular chromosome. Replication then proceeds around the entire circle of the chromosome in each direction from the two replication forks, resulting in two DNA molecules.
Many Proteins Work Together to Replicate the Chromosome
Replication is coordinated and carried out by a host of specialized...
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Replication in Eukaryotes01:29

Replication in Eukaryotes

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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.
Many Proteins Orchestrate Replication at the Origin
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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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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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DNA Replication02:40

DNA Replication

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DNA replication involves the separation of the two strands of the double helix, with each strand serving as a template from which the new complementary strand is copied.  After replication, each double-stranded DNA includes one parental or “old” strand and one “new” strand. This is known as semiconservative replication. The resulting DNA molecules have the same sequence and are divided equally into the two daughter cells.
Replication in Prokaryotes
DNA replication...
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Related Experiment Video

Updated: Jul 1, 2025

Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
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Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase

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Fork coupling directs DNA replication elongation and termination.

Yang Liu1,2, Zhengrong Zhangding1, Xuhao Liu1

  • 1The MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Genome Editing Research Center, Peking University; Beijing 100871, China.

Science (New York, N.Y.)
|March 14, 2024
PubMed
Summary
This summary is machine-generated.

Researchers discovered "fountain-like" DNA structures linking replication forks, revealing how DNA duplication is coordinated. This process, crucial for genome stability, is disrupted in cancers, leading to genomic deletions.

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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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Visualization of DNA Replication in the Vertebrate Model System DT40 using the DNA Fiber Technique
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Visualization of DNA Replication in the Vertebrate Model System DT40 using the DNA Fiber Technique

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Last Updated: Jul 1, 2025

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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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Visualization of DNA Replication in the Vertebrate Model System DT40 using the DNA Fiber Technique
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Area of Science:

  • Molecular Biology
  • Genomics
  • Cell Biology

Background:

  • Eukaryotic genome duplication requires timely initiation of DNA replication at multiple origins.
  • Replication forks progress bidirectionally from origins and terminate upon meeting convergent forks.
  • Understanding the spatial coordination of replication forks is essential for genome integrity.

Purpose of the Study:

  • To investigate the coordination and spatial organization of DNA replication forks.
  • To capture and analyze chromatin interactions involving nascent DNA during replication.

Main Methods:

  • Development of a novel replication-associated in situ HiC method.
  • Analysis of chromatin contacts involving nascent DNA in human and mouse genomes.

Main Results:

  • Identification of over 2000 chromatin contact structures resembling fountains, indicating coupled DNA replication forks.
  • Demonstration that replication fork interactions occur between sister forks and forks from distinct origins to facilitate termination.
  • Observation that termination-associated chromatin fountains are sensitive to replication stress and linked to genomic deletions in cancers.

Conclusions:

  • The study reveals a novel spatial organization of DNA replication forks within the chromatin context.
  • Replication fork coupling plays a critical role in predetermined replication termination and genome stability.
  • Disruption of replication fork coordination and associated structures contributes to genomic instability in cancer.