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DNA in a human cell is almost 2m long and it is packed inside a tiny nucleus that is only a few microns in diameter. The level of compaction of DNA inside the nucleus is astonishing. It is organized into several sequentially higher levels of compaction to fit into such a tiny space. The most compact form of DNA is a chromosome that can be seen under a microscope in a dividing cell.
DNA is wound twice around a protein complex called histone core, that consist of 8 histone proteins. This complex...
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Human DNA is almost two meters long. However, it is compressed inside a tiny nucleus measuring only a few microns in diameter. To make this degree of compaction possible, DNA is organized into several sequential levels so that it can fit into such a tiny space. The most compact form of DNA is a chromosome that can be seen under a microscope in a dividing cell.
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Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
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Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
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Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
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Updated: Feb 3, 2026

Assembly of Nucleosomal Arrays from Recombinant Core Histones and Nucleosome Positioning DNA
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La periodicidad de la mutación somática y germinal sigue la orientación del surco menor del ADN alrededor de los

Oriol Pich1, Ferran Muiños1, Radhakrishnan Sabarinathan1

  • 1Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.

Cell
|November 3, 2018
PubMed
Resumen

Los nucleosomas, las estructuras fundamentales del ADN, crean una periodicidad de tasa de mutación de 10 pares de bases (bp). Este patrón, visto en tumores y poblaciones, surge de la orientación de ranuras menores del ADN que influyen en el daño y la reparación.

Palabras clave:
Daño en el ADNReparación del ADNPeriodicidad WWVariabilidad de la línea germinalPosicionamiento de los nucleosomasmutaciones somáticasmutaciones tumorales

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Área de la Ciencia:

  • La genómica
  • Biología molecular
  • La epigenética

Sus antecedentes:

  • Las tasas de mutación en todo el genoma están influenciadas por las características de la cromatina.
  • Los nucleosomas son las estructuras de cromatina primarias en los genomas eucariotas.

Objetivo del estudio:

  • Investigar el impacto de los nucleosomas en la generación de mutaciones.
  • Identificar patrones en las tasas de mutación relacionadas con la estructura del nucleosoma.

Principales métodos:

  • Análisis de las tasas de mutación somática en cohortes de tumores.
  • Examen de la variación genética en las poblaciones humanas y de Arabidopsis.
  • Genómica comparativa para estudiar la divergencia de las especies.

Principales resultados:

  • Se descubrió una fuerte periodicidad de 10 pares de bases (bp) en las tasas de mutación somática dentro de los nucleosomas.
  • Esta periodicidad se correlaciona con la orientación de la ranura menor del ADN en relación con las histonas.
  • Se encontraron patrones periódicos similares en la variación genética de la línea germinal y la divergencia entre especies.
  • Los procesos mutacionales en los tumores influyen en la fuerza y la fase de esta periodicidad.

Conclusiones:

  • La estructura del nucleosoma impone una periodicidad de 10 bp en las tasas de mutación del ADN.
  • Este fenómeno afecta tanto a las mutaciones somáticas como germinales en los eucariotas.
  • El daño y la reparación diferencial del ADN basados en la orientación de ranuras menores probablemente impulsan esta periodicidad e influyen en la composición del genoma.