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DNA Replication02:40

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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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La acetilación de la cohesión acelera la bifurcación de la replicación.

Marie-Emilie Terret1, Rebecca Sherwood, Sadia Rahman

  • 1Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.

Nature
|November 13, 2009
PubMed
Resumen

El cargador de pinzas del factor de replicación C (RFC) -CTF18 regula la velocidad de la horquilla de replicación y la acetilación de la cohesión, que es crucial para la duplicación del genoma y la prevención de daños en el ADN. Este estudio revela un nuevo mecanismo que implica la modificación de la cohesión para la progresión de la bifurcación.

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Área de la Ciencia:

  • Biología Molecular Biología Molecular
  • Biología celular Biología celular.
  • Genética La genética.

Sus antecedentes:

  • La cohesina enlaza las cromatidas hermanas y regula la accesibilidad de la cromatina.
  • Las horquillas de replicación deben superar los obstáculos asociados a la cohesión durante la replicación del ADN.
  • El mecanismo por el cual las horquillas de replicación navegan por la cohesión es en gran medida desconocido.

Objetivo del estudio:

  • Para investigar el papel del cargador de pinzas RFC-CTF18 en la progresión de la horquilla de replicación.
  • Para dilucidar la función de la acetilación de la cohesina en la replicación del ADN.
  • Comprender el vínculo entre la regulación de la cohesión y la estabilidad del genoma.

Principales métodos:

  • Análisis de una sola molécula en células humanas.
  • Investigación de la acetilación de la cohesina y su impacto en las horquillas de replicación.
  • Análisis de células con mutaciones en las cohesina acetiltransferasas (ESCO1, ESCO2) y células de pacientes con síndrome de Roberts.

Principales resultados:

  • RFC-CTF18 controla la velocidad de la horquilla de replicación, el espaciado y el reinicio, y es esencial para la acetilación SMC3 y la cohesión de las cromatidas hermanas.
  • La acetilación de la cohesina es crítica para la procesividad de la horquilla de replicación; su ausencia conduce a horquillas lentas.
  • El estado de acetilación de SMC3 dicta la velocidad de bifurcación mediante la modulación de la interacción de la cohesina con WAPL y PDS5A.

Conclusiones:

  • Se describe un nuevo mecanismo para la progresión de la horquilla dependiente del cargador de la abrazadera mediada por la modificación post-traducional de la cohesión y la remodelación estructural.
  • La desregulación de este proceso dependiente de la acetilación de la cohesina conduce a la acumulación de daño en el ADN.
  • Los defectos en esta vía pueden contribuir a las cohesinopatías como el síndrome de Roberts.