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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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Replication in Prokaryotes01:32

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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
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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.
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Restarting Stalled Replication Forks02:37

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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.
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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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El acoplamiento de bifurcación dirige el alargamiento y la terminación de la replicación del ADN

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
Resumen
Este resumen es generado por máquina.

Los investigadores descubrieron estructuras de ADN "similares a fuentes" que unen las bifurcaciones de la replicación, revelando cómo se coordina la duplicación del ADN. Este proceso, crucial para la estabilidad del genoma, se interrumpe en los cánceres, lo que lleva a deleciones genómicas.

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Área de la Ciencia:

  • Biología molecular
  • La genómica
  • Biología celular

Sus antecedentes:

  • La duplicación del genoma eucariota requiere el inicio oportuno de la replicación del ADN en múltiples orígenes.
  • Las bifurcaciones de replicación progresan bidireccionalmente desde los orígenes y terminan cuando se encuentran con bifurcaciones convergentes.
  • Comprender la coordinación espacial de las bifurcaciones de replicación es esencial para la integridad del genoma.

Objetivo del estudio:

  • Para investigar la coordinación y la organización espacial de las bifurcaciones de la replicación del ADN.
  • Para capturar y analizar las interacciones de cromatina que involucran el ADN naciente durante la replicación.

Principales métodos:

  • Desarrollo de un nuevo método de HiC asociado a la replicación in situ.
  • Análisis de los contactos de cromatina que involucran el ADN naciente en los genomas de humanos y ratones.

Principales resultados:

  • Identificación de más de 2000 estructuras de contacto de cromatina que se asemejan a fuentes, lo que indica horquillas de replicación de ADN acopladas.
  • Demostrar que las interacciones de bifurcación de replicación ocurren entre bifurcaciones hermanas y bifurcaciones de orígenes distintos para facilitar la terminación.
  • Observación de que las fuentes de cromatina asociadas a la terminación son sensibles al estrés de replicación y están relacionadas con las deleciones genómicas en los cánceres.

Conclusiones:

  • El estudio revela una nueva organización espacial de las bifurcaciones de la replicación del ADN dentro del contexto de la cromatina.
  • El acoplamiento de la bifurcación de replicación juega un papel crítico en la terminación predeterminada de la replicación y la estabilidad del genoma.
  • La interrupción de la coordinación de la bifurcación de replicación y las estructuras asociadas contribuye a la inestabilidad genómica en el cáncer.