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Related Concept Videos

Histone Variants at the Centromere02:30

Histone Variants at the Centromere

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 variants are also...
Meiosis II02:02

Meiosis II

Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for meiosis II are similar to mitosis, except that meiosis II occurs in haploid cells, whereas mitosis occurs in diploid cells.
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

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.
At the onset of anaphase, separase, a proteolytic enzyme, is...
Attachment of Sister Chromatids02:57

Attachment of Sister Chromatids

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 of a...
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

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.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Cohesins02:20

Cohesins

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.
Cohesin complexes in Meiotic Division
Meiosis involves two distinct rounds of chromosomal segregation and cell divisions— Meiosis I followed by Meiosis II – producing four daughter cells. Meiosis I includes the separation of homologous...

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Related Experiment Video

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Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins
05:35

Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins

Published on: March 3, 2016

γH2A-binding protein Brc1 affects centromere function in fission yeast.

Si Young Lee1, Sophie Rozenzhak, Paul Russell

  • 1Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.

Molecular and Cellular Biology
|January 30, 2013
PubMed
Summary

Brc1 protein stabilizes stalled replication forks in fission yeast, which is crucial for maintaining pericentromeric heterochromatin and ensuring accurate chromosome segregation during cell division.

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Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins
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Use of Time-Lapse Microscopy and Stage-Specific Nuclear Depletion of Proteins to Study Meiosis in S. cerevisiae
07:48

Use of Time-Lapse Microscopy and Stage-Specific Nuclear Depletion of Proteins to Study Meiosis in S. cerevisiae

Published on: October 11, 2022

Area of Science:

  • Cell Biology
  • Genetics
  • Epigenetics

Background:

  • Pericentromeric heterochromatin is vital for centromere function and is transmitted via RNA interference (RNAi).
  • Histone H2A phosphorylation (γH2A) recruits Brc1 to pericentromeric heterochromatin during S phase.
  • Brc1's role in centromere function, beyond stabilizing replication forks, was previously unknown.

Purpose of the Study:

  • To investigate the role of Brc1 in pericentromeric heterochromatin maintenance and centromere function.
  • To determine if Brc1's replication fork stabilization activity influences centromere integrity.
  • To elucidate the interplay between Brc1, γH2A, and chromosome segregation.

Main Methods:

  • Localization studies of Brc1 in fission yeast pericentromeric heterochromatin.
  • Assays for histone modifications (H3K9me2) and gene silencing.
  • Sensitivity tests to microtubule-destabilizing agents (thiabendazole).
  • Analysis of chromosome missegregation.
  • Genetic manipulation of histone H2A phosphorylation sites.

Main Results:

  • Brc1 localizes to pericentromeric heterochromatin during S phase and enhances H3K9me2 and gene silencing.
  • Loss of Brc1 leads to increased sensitivity to thiabendazole and chromosome missegregation.
  • Brc1 retains function independently of γH2A binding.
  • Eliminating histone H2A serine-121 sensitizes cells lacking γH2A or Brc1 to replication stress.

Conclusions:

  • Brc1-mediated stabilization of stalled replication forks is essential for efficient pericentromeric heterochromatin transmission.
  • Accurate transmission of pericentromeric heterochromatin is required for proper chromosome segregation during mitosis.
  • Brc1 plays a critical role in linking replication fork stability to centromere function and genomic stability.