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Related Concept Videos

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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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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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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Spindle assembly occurs through three, often coexisting, pathways – the centrosome-mediated pathway, the chromatin-mediated pathway, and the microtubule-mediated pathway – collectively contributing to form a robust spindle apparatus.
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Assembly of Complex Microtubule Structures01:32

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Complex microtubule structures are present in resting cells and in dividing cells. In resting cells, they are responsible for maintaining the cellular architecture, tracks for intracellular transport, positioning of organelles, assembly of cilia and flagella. They mediate the bipolar spindle assembly for chromosomal segregation and positioning of the cell division plate in dividing cells. The formation of microtubule complex structures depends on the cell type, cell stage, and cell function.
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Related Experiment Video

Updated: Jun 22, 2025

Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins
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Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins

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Structural basis for Mis18 complex assembly and its implications for centromere maintenance.

Reshma Thamkachy1, Bethan Medina-Pritchard1, Sang Ho Park2

  • 1Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, EH9 3BF, UK.

EMBO Reports
|July 1, 2024
PubMed
Summary
This summary is machine-generated.

The Mis18 complex, crucial for centromere identity, assembles into a hetero-octamer. Mis18α alone can deposit CENP-A, but Mis18β is vital for optimal CENP-A loading and centromere maintenance.

Keywords:
CENP-ACentromereCentromere InheritanceIntegrative Structural AnalysisMis18 Complex

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Related Experiment Videos

Last Updated: Jun 22, 2025

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Mass Spectrometry Analysis to Identify Ubiquitylation of EYFP-tagged CENP-A EYFP-CENP-A
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Area of Science:

  • Cell Biology
  • Epigenetics
  • Structural Biology

Background:

  • The centromere is essential for chromosome segregation, defined by the histone H3 variant CENP-A.
  • Maintaining CENP-A levels is critical for centromere identity and function.
  • The Mis18 complex (Mis18α, Mis18β, Mis18BP1) is a key regulator of CENP-A deposition.

Purpose of the Study:

  • To elucidate the structural basis of Mis18 complex assembly.
  • To understand the functional roles of Mis18 subunits in CENP-A loading and centromere maintenance.
  • To identify structural determinants governing cell cycle-controlled Mis18 function.

Main Methods:

  • Multi-pronged structural characterization of the Mis18 complex.
  • Biochemical assays to analyze complex assembly and subunit interactions.
  • Structure-guided mutagenesis to assess the function of structural elements.
  • Cell cycle analysis and centromere function assays.

Main Results:

  • The Mis18 complex forms a stable hetero-octamer (4 Mis18α, 2 Mis18β, 2 Mis18BP1) through multiple hetero- and homo-oligomeric interfaces.
  • Structural analysis revealed key interfaces essential for complex assembly and stability.
  • Mis18α can independently associate with centromeres and facilitate CENP-A deposition.
  • Mis18β is indispensable for achieving the optimal CENP-A loading levels required for centromere identity.

Conclusions:

  • The structure of the Mis18 complex provides mechanistic insights into its assembly and function.
  • Differential roles of Mis18 subunits in CENP-A deposition and centromere maintenance were uncovered.
  • This study highlights the importance of precise CENP-A loading for preserving centromere identity.