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Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
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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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During mitosis, chromosome movements occur through the interplay of multiple piconewton level forces. In prometaphase, these forces help in chromosome assembly or congression at the equatorial plane, eventually leading to their alignment at the metaphase plate. The forces acting on the chromosomes are space and time-dependent; therefore, they vary with the position of the chromosomes as the cell progresses through mitosis. 
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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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The primary microtubule organizing center (MTOC) in animal cells is the centrosome. A centrosome has two cylindrical centrioles at its core. Each centriole consists of nine sets of three microtubules held together by proteins. The centrioles are positioned at right angles to each other and surrounded by a shapeless protein cloud called the pericentriolar matrix, or pericentriolar material (PCM).
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Las vías paralelas para reclutar proteínas efectoras determinan el impulso y la supresión del centrómero

Tomohiro Kumon1, Jun Ma1, R Brian Akins1

  • 1Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.

Cell
|August 25, 2021
PubMed
Resumen

El ADN centromero egoísta impulsa la herencia sesgada. Las proteínas centrómeras evolucionan para contrarrestar este impulso suprimiendo las vías cinetocóricas y favoreciendo las vías de la heterocromatina, asegurando una transmisión cromosómica estable.

Palabras clave:
el centromeroLa carrera armamentista evolutivaLa heterocromatinaEl kinetochorroUnidad meióticaLos elementos genéticos egoístas

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Área de la Ciencia:

  • La genética
  • Biología evolutiva
  • Biología molecular

Sus antecedentes:

  • Las secuencias de ADN centromero egoístas pueden sesgar su transmisión durante la meiosis femenina, un fenómeno conocido como impulso centromero.
  • La teoría evolutiva postula que las proteínas centroméricas coevolucionan para mitigar las consecuencias negativas de la unidad centromérica.

Objetivo del estudio:

  • Investigar los mecanismos moleculares por los cuales las proteínas centroméricas suprimen el impulso centromérico en modelos de ratón híbrido.
  • Determinar las funciones de las vías cinetocóricas y de la heterocromatina en la regulación de las diferencias funcionales entre los centrómeros maternos y paternos.

Principales métodos:

  • Se utilizaron modelos de ratones híbridos con centrómeros maternos y paternos genéticamente distintos.
  • Investigó la explotación del ADN centromero egoísta de las vías cinetocóricas y el reclutamiento de proteínas desestabilizadoras de microtúbulos.
  • Interrupción de la vía cinetocórica a través del alelo CENP-C y de la vía heterocromatina a través de la deleción de CENP-B.
  • Realizó análisis de evolución molecular en genomas de murinos.

Principales resultados:

  • El ADN centromero egoísta explota una vía cinetocórica para impulsar, reclutando proteínas desestabilizadoras de microtúbulos.
  • Una vía paralela de heterocromatina suprime las diferencias funcionales entre los centrómeros.
  • La interrupción de CENP-C redujo las diferencias de centrómeros, mientras que la deleción de CENP-B las amplificó.
  • La evolución molecular reveló cambios adaptativos en las proteínas de ambas vías.

Conclusiones:

  • Las proteínas centrómeras han evolucionado para suprimir la vía cinetocórica explotada por el ADN egoísta.
  • La vía de la heterocromatina actúa para igualar los centrómeros, contrarrestando el impulso de los centrómeros.
  • La evolución recurrente tiene como objetivo minimizar la explotación de la vía cinetocórica mientras se mantienen las funciones esenciales del centrómero.