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Related Concept Videos

Cohesins02:20

Cohesins

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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...
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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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Homologous Recombination02:31

Homologous Recombination

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The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
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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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Condensins02:15

Condensins

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Condensins are large protein complexes that use ATP to fuel the assembly of chromosomes during mitosis. They transform the tangled, shapeless mass of post-interphase DNA into individualized chromosomes by compacting, organizing, and segregating chromosomal DNA.
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Restarting Stalled Replication Forks02:37

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DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
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Related Experiment Video

Updated: Jul 1, 2025

Using Fluorescence In Situ Hybridization FISH to Monitor the State of Arm Cohesion in Prometaphase and Metaphase I Drosophila Oocytes
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Sister chromatid cohesion establishment during DNA replication termination.

George Cameron1, Dominika T Gruszka1, Rhian Gruar2

  • 1The Francis Crick Institute, London, UK.

Science (New York, N.Y.)
|March 14, 2024
PubMed
Summary

Sister chromatid cohesion is established during DNA replication termination, not before. The study reveals cohesin complexes are pushed by replication forks and remain on nascent DNA after CMG helicase disassembly.

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Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method
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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Sister chromatid cohesion, mediated by the cohesin complex, is crucial for accurate chromosome segregation during cell division.
  • The precise coordination between cohesin loading, DNA replication, and the establishment of cohesion remains incompletely understood.

Purpose of the Study:

  • To investigate how cohesin complexes interact with the DNA replication machinery.
  • To elucidate the mechanism by which sister chromatid cohesion is established during DNA replication.

Main Methods:

  • Visualizing replication forks interacting with preloaded cohesin complexes in real-time.
  • Analyzing the role of CMG (CDC45-MCM2-7-GINS) helicase disassembly in replication termination and cohesion establishment in budding yeast.

Main Results:

  • Replication forks push cohesin complexes towards converging replication forks, rather than cohesin remaining behind.
  • Cohesin persists on nascent DNA after replication termination, ensuring sister chromatid cohesion.
  • Disassembly of the CMG helicase during replication termination is essential for establishing proper cohesion.

Conclusions:

  • Sister chromatid cohesion is established during the termination stage of DNA replication.
  • A novel model is proposed where cohesin is actively managed by the replisome during replication and secured upon termination.