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Related Concept Videos

Histone Variants at the Centromere02:30

Histone Variants at the Centromere

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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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Attachment of Sister Chromatids02:57

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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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Separation of Sister Chromatids02:17

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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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Centrosome Duplication02:25

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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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Chromatin Position Affects Gene Expression02:35

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Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
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Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins
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Parallel pathways for recruiting effector proteins determine centromere drive and suppression.

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
Summary

Selfish centromere DNA drives biased inheritance. Centromere proteins evolve to counteract this drive by suppressing kinetochore pathways and favoring heterochromatin pathways, ensuring stable chromosome transmission.

Keywords:
centromereevolutionary arms raceheterochromatinkinetochoremeiotic driveselfish genetic elements

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Area of Science:

  • Genetics
  • Evolutionary Biology
  • Molecular Biology

Background:

  • Selfish centromere DNA sequences can bias their transmission during female meiosis, a phenomenon known as centromere drive.
  • Evolutionary theory posits that centromere proteins co-evolve to mitigate the negative consequences of centromere drive.

Purpose of the Study:

  • To investigate the molecular mechanisms by which centromere proteins suppress centromere drive in hybrid mouse models.
  • To determine the roles of kinetochore and heterochromatin pathways in regulating functional differences between maternal and paternal centromeres.

Main Methods:

  • Utilized hybrid mouse models with genetically distinct maternal and paternal centromeres.
  • Investigated selfish centromere DNA's exploitation of kinetochore pathways and recruitment of microtubule-destabilizing proteins.
  • Disrupted kinetochore pathway via CENP-C allele and heterochromatin pathway via CENP-B deletion.
  • Performed molecular evolution analyses on Murinae genomes.

Main Results:

  • Selfish centromere DNA exploits a kinetochore pathway for drive, recruiting microtubule-destabilizing proteins.
  • A parallel heterochromatin pathway suppresses functional differences between centromeres.
  • Disrupting CENP-C reduced centromere differences, while CENP-B deletion amplified them.
  • Molecular evolution revealed adaptive changes in proteins of both pathways.

Conclusions:

  • Centromere proteins have evolved to suppress the kinetochore pathway exploited by selfish DNA.
  • The heterochromatin pathway acts to equalize centromeres, counteracting centromere drive.
  • Recurrent evolution aims to minimize kinetochore pathway exploitation while maintaining essential centromere functions.