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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.
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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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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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Updated: Jan 17, 2026

Author Spotlight: Investigating the Motion Dynamics of the Eukaryotic Replisome Components at the Single-Molecule Level
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Replisome passage through the cohesin ring.

Samson Glaser1, Maxim I Molodtsov2, John F X Diffley3

  • 1Chromosome Replication Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Chromosome Segregation Laboratory, The Francis Crick Institute, London NW1 1AT, UK.

Cell
|September 17, 2025
PubMed
Summary
This summary is machine-generated.

Eukaryotic replicative helicases (CMG) pass through cohesin rings, trapping replicated DNA. This discovery reveals a direct link between DNA replication and chromosome segregation, impacting cell division.

Keywords:
DNA replicationchromosome segregationcohesinsingle-molecule fluorescence microscopysister chromatid cohesion

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The cohesin complex encircles sister chromatids post-replication, ensuring accurate chromosome segregation during cell division.
  • The mechanism by which replication machinery interacts with cohesin, specifically whether replisomes can pass through cohesin rings, remained uncharacterized.

Purpose of the Study:

  • To directly visualize and investigate the interaction between the eukaryotic replicative helicase (CMG) and cohesin rings.
  • To determine if replisomes can successfully traverse cohesin rings during DNA replication.
  • To elucidate the role of DNA polymerases in facilitating replisome passage through cohesin.

Main Methods:

  • Biochemical reconstitution of the DNA replication machinery and cohesin complex.
  • Single-molecule fluorescence microscopy to observe real-time replisome-cohesin encounters.

Main Results:

  • The translocating eukaryotic replicative helicase (Cdc45-Mcm2-7-GINS or CMG) readily passes through cohesin rings.
  • Fully reconstituted replisomes successfully pass through cohesin rings, leaving both newly synthesized DNA strands entrapped.
  • DNA polymerases α and ε play a crucial role in aiding replisome passage through cohesin rings.

Conclusions:

  • Replisome passage through cohesin rings is a key mechanism linking genome replication to chromosome segregation.
  • This finding challenges previous assumptions about the roles of cohesion establishment factors in this process.
  • The study provides direct evidence for a fail-safe mechanism ensuring co-entrapment of replication products within cohesin.