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Chromosome Replication02:31

Chromosome Replication

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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 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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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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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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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.
The centromere is a DNA sequence that links sister chromatids. This is also where kinetochores, protein complexes to which spindle microtubules attach, are constructed after the chromosome is replicated. The kinetochores allow the spindle microtubules to move the chromosomes within the cell during cell division.
Telomeres consist of non-coding repetitive nucleotide...
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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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Video Experimental Relacionado

Updated: Jun 6, 2025

Author Spotlight: Investigating the Motion Dynamics of the Eukaryotic Replisome Components at the Single-Molecule Level
10:11

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

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Mecanismos múltiples para la concesión de licencias para los orígenes de la replicación humana

Ran Yang1, Olivia Hunker1, Marleigh Wise1

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

Nature
|November 28, 2024
PubMed
Resumen
Este resumen es generado por máquina.

La carga de MCM humano en el ADN implica mecanismos flexibles distintos de la levadura, que utilizan la autodimerización ORC6 y MCM2-7 para la licencia de origen de la replicación y la resistencia al estrés celular.

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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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Área de la Ciencia:

  • Biología molecular
  • Biología celular
  • La bioquímica

Sus antecedentes:

  • El inicio de la replicación del ADN requiere la carga de la helicasa replicativa MCM2-7 en el ADN.
  • El complejo de reconocimiento de origen (ORC) y los cocargadores depositan MCM2-7 como un hexámero doble para licenciar los orígenes de replicación.
  • Los mecanismos de carga de MCM en eucariotas multicelulares no se comprenden bien, a diferencia de la levadura.

Objetivo del estudio:

  • Para reconstituir y dilucidar bioquímicamente la vía de carga de MCM en humanos.
  • Investigar el papel de ORC6 en la carga de MCM en humanos.
  • Identificar los intermediarios y los mecanismos de formación de hexámero doble de MCM.

Principales métodos:

  • Reconstitución bioquímica de la vía de carga de MCM en el hombre.
  • Microscopía electrónica de transmisión (TEM) para visualizar los intermedios de carga.
  • Análisis del papel de ORC6 en la carga de MCM.

Principales resultados:

  • La carga de MCM en humanos es mejorada, no esencial, por ORC6, que difiere de la levadura.
  • Identificamos un hexámero intermedio de MCM cargado con ADN.
  • Se han demostrado múltiples vías para la formación de hexámero doble de MCM, incluida la autodimerización mediada por ORC y MCM.
  • Se han caracterizado distintos complejos MCM-ORC (MO) en humanos frente a la levadura.

Conclusiones:

  • La carga de MCM humano exhibe flexibilidad a través de múltiples mecanismos, lo que potencialmente mejora la resistencia al estrés de replicación.
  • Los intermediarios y vías identificados proporcionan información sobre el inicio de la replicación del ADN eucariota.
  • El sistema de reconstitución facilita futuros estudios sobre el inicio de la replicación y los eventos acoplados.