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Related Concept Videos

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.
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Chromosome Replication02:31

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Before a cell can divide, it must accurately replicate all of its chromosomes, including the DNA and its associated histone and non-histone proteins.  This process begins at numerous origins of replication during the S phase of the cell cycle in each of a cell’s chromosomes simultaneously. Certain nucleotides can act as origins of replication, but these sequences are not well defined - especially in complex, multi-cellular, eukaryotic species. The length of DNA that spans an origin...
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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.
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Chromosome Structure02:40

Chromosome Structure

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A functional eukaryotic chromosome must contain three elements: a centromere, telomeres, and numerous origins of replication.
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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.
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S-Cdk Initiates DNA Replication02:38

S-Cdk Initiates DNA Replication

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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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Related Experiment Video

Updated: Jun 28, 2025

Author Spotlight: Investigating the Motion Dynamics of the Eukaryotic Replisome Components at the Single-Molecule Level
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Author Spotlight: Investigating the Motion Dynamics of the Eukaryotic Replisome Components at the Single-Molecule Level

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Multiple pathways for licensing human replication origins.

Ran Yang1, Olivia Hunker1, Marleigh Wise1

  • 1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.

Biorxiv : the Preprint Server for Biology
|April 22, 2024
PubMed
Summary
This summary is machine-generated.

Human DNA replication licensing uses two pathways for loading MCM2-7 helicases, with Orc6 enhancing but not essential for origin recognition complex (ORC) function. This redundancy ensures efficient DNA replication and resilience against stress.

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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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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • DNA replication initiation requires loading of replicative helicases onto DNA.
  • The MCM2-7 helicase motor is loaded by the origin recognition complex (ORC) and co-loaders to license replication origins in eukaryotes.
  • Mechanisms of origin licensing in higher eukaryotes are not well understood, unlike in yeast.

Approach:

  • Biochemical reconstitution and electron microscopy (EM) were used to study the human MCM loading pathway.
  • Investigated the role of the ORC's Orc6 subunit in human MCM loading.
  • Identified key intermediates in MCM double hexamer formation.

Key Points:

  • Human MCM loading can occur independently of the Orc6 subunit, which enhances but is not essential.
  • An abundant single MCM hexamer intermediate was identified.
  • Two distinct pathways for MCM double hexamer formation were observed: one Orc6-facilitated and one Orc6-independent.

Conclusions:

  • Human MCM loading exhibits pathway redundancy, with an Orc6-independent route involving MCM hexamer dimerization.
  • This redundancy likely enhances resilience against replication stress by ensuring sufficient origin licensing.
  • The study provides a foundation for future research on DNA replication initiation in higher eukaryotes.