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The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
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The mitotic spindle—or spindle apparatus—is a eukaryotic, cytoskeletal structure made up of long protein fibers called microtubules. Formed during cell division, the spindle separates sister chromatids and moves them to opposite ends of a parental cell, where the now individual chromosomes are distributed to two daughter cell nuclei.
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As cells progress into mitosis, the nuclear envelope breaks down, and the condensed chromosomes are exposed to the array of bipolar microtubules of the mitotic spindle. The kinetochore, a large, disc-shaped protein complex, is present at the centromere region of the sister chromatids and acts as a binding site for the microtubules.  Usually, the plus-end of a single microtubule is embedded within the kinetochore. However, some kinetochores first establish lateral contact with the side-wall...
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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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At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
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Cohesin protein complexes are a molecular glue that holds two sister chromatids together. They play an important role both in mitosis and meiosis. In mitosis, all cohesin complexes present on the chromosomes are removed before the start of the anaphase stage.
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Marcado mitótico por subunidades SWI/SNF

Zhexin Zhu1, Xiaolong Chen2, Ao Guo3

  • 1Division of Molecular Oncology, Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA. zhexin.zhu@stjude.org.

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|May 24, 2023
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Resumen

La identidad celular se basa en una memoria mitótica. Los complejos SWI / SNF de mamíferos, específicamente SMARCE1, actúan como marcadores mitóticos cruciales, asegurando la expresión genética correcta y el destino celular durante la división celular.

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Área de la Ciencia:

  • La epigenética
  • Biología celular
  • Biología molecular

Sus antecedentes:

  • La diferenciación celular requiere la transmisión de información de estado a través de la mitosis.
  • Los complejos SWI / SNF de mamíferos regulan la identidad celular a través de la remodelación de la cromatina.
  • El papel de SWI/SNF en la memoria del destino celular durante la mitosis no estaba claro anteriormente.

Objetivo del estudio:

  • Investigar el papel de los complejos SWI/SNF en el mantenimiento de la identidad celular durante la división celular.
  • Para determinar si las subunidades SWI/SNF funcionan como marcadores mitóticos.
  • Aclarar el mecanismo por el cual SWI/SNF salvaguarda el destino celular durante la mitosis.

Principales métodos:

  • Análisis de la localización de las subunidades SWI/SNF (SMARCE1, SMARCB1) durante la mitosis.
  • Análisis de la expresión génica después de la ablación de SMARCE1 en células madre embrionarias de ratón.
  • Evaluación de la ocupación de marcadores establecida y la diferenciación neuronal.

Principales resultados:

  • Las subunidades del núcleo SWI/SNF SMARCE1 y SMARCB1 se unen a los promotores durante la mitosis, no a los potenciadores.
  • Esta unión del promotor es esencial para la reactivación del gen después de la mitosis.
  • La ablación de SMARCE1 durante la mitosis interrumpe la expresión génica y conduce a una diferenciación neural aberrante.

Conclusiones:

  • La subunidad SWI/SNF SMARCE1 funciona como un marcador mitótico.
  • SMARCE1 es crítico para mantener la fidelidad epigenética hereditaria durante la división celular.
  • Este mecanismo asegura una determinación precisa del destino celular y la reprogramación de la transcripción.