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Before a cell can divide, it must accurately replicate all of its chromosomes, including the DNA and its associated histone and non-histone proteins.  This process begins at numerous origins of replication during the S phase of the cell cycle in each of a cell’s chromosomes simultaneously. Certain nucleotides can act as origins of replication, but these sequences are not well defined - especially in complex, multi-cellular, eukaryotic species. The length of DNA that spans an origin of...
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Related Experiment Video

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Generation of Genome-wide Chromatin Conformation Capture Libraries from Tightly Staged Early Drosophila Embryos
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RepliSage: a stochastic graph-based framework for 3D chromatin modeling across the cell cycle.

Sevastianos Korsak1,2, Krzysztof H Banecki1,2, Abhishek Agarwal2

  • 1Warsaw University of Technology, Faculty of Mathematics and Information Science, Laboratory of Bioinformatics and Computational Genomics, 00-662 Warsaw, Poland.

Nucleic Acids Research
|June 22, 2026
PubMed
Summary
This summary is machine-generated.

We developed RepliSage, a novel biophysical model that captures dynamic chromatin changes throughout the cell cycle. This framework integrates DNA replication, loop extrusion, and compartmentalization for a comprehensive understanding of genome organization.

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Area of Science:

  • Cell Biology
  • Biophysics
  • Genomics

Background:

  • Chromatin dynamics are essential for cell cycle processes like DNA replication and chromosome segregation.
  • Existing biophysical models lack a comprehensive description of chromatin transitions across the entire cell cycle.

Purpose of the Study:

  • To present RepliSage, a multi-scale framework modeling chromatin dynamics throughout the cell cycle.
  • To integrate DNA replication, loop extrusion, and compartmentalization into a unified biophysical model.

Main Methods:

  • Simulated replication fork progression using single-cell replication timing data.
  • Employed Monte Carlo modeling for loop extrusion and epigenetic state transitions.
  • Utilized OpenMM for 3D reconstruction of chromatin architecture.

Main Results:

  • RepliSage captures distinct chromatin dynamics in G1, S, and mitosis phases.
  • Replication forks are modeled as dynamic barriers interacting with loop extrusion factors during S phase.
  • Condensins drive chromatin compaction and segregation during mitosis.

Conclusions:

  • RepliSage is the first framework to dynamically couple DNA replication, loop extrusion, and compartmentalization across the cell cycle.
  • The model provides a platform to investigate the impact of replication stress on genome organization.
  • RepliSage successfully reproduces known chromatin structural transitions and was validated with extensive datasets.