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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.
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
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Replication in Eukaryotes02:31

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Overview
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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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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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Protein Complexes with Interchangeable Parts01:57

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Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
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Related Experiment Video

Updated: Apr 16, 2026

Combining X-Ray Crystallography with Small Angle X-Ray Scattering to Model Unstructured Regions of Nsa1 from S. Cerevisiae
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Combining X-Ray Crystallography with Small Angle X-Ray Scattering to Model Unstructured Regions of Nsa1 from S. Cerevisiae

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Crystal structure of the eukaryotic origin recognition complex.

Franziska Bleichert1, Michael R Botchan2, James M Berger1

  • 1Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.

Nature
|March 13, 2015
PubMed
Summary
This summary is machine-generated.

The origin recognition complex (ORC) structure reveals a novel mechanism for controlling DNA replication initiation. This structure suggests ORC can switch between active and inhibited states, impacting cell cycle regulation.

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Area of Science:

  • Structural biology
  • Molecular biology
  • Cell cycle regulation

Background:

  • Cellular DNA replication initiation is crucial for genomic stability.
  • The heterohexameric origin recognition complex (ORC) orchestrates replication onset in eukaryotes.

Purpose of the Study:

  • To determine the crystal structure of Drosophila ORC.
  • To elucidate the structural basis for ORC function in DNA replication initiation.

Main Methods:

  • X-ray crystallography at 3.5 Å resolution.
  • Structural analysis of the 270 kDa ORC core complex.

Main Results:

  • The ORC structure reveals a two-layered ring with winged-helix and AAA+ domains.
  • Unanticipated inter-domain swapping and a quasi-spiral DNA-binding channel were observed.
  • A significant rotation of the Orc1 AAA+ domain suggests a mechanism for autoinhibition.

Conclusions:

  • Drosophila ORC encircles DNA and engages the MCM2-7 complex for helicase loading.
  • The structure indicates ORC can transition between active and autoinhibited conformations.
  • This conformational switching offers a novel regulatory mechanism for cell cycle control.