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Related Concept Videos

The DNA Replication Fork01:02

The DNA Replication Fork

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An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork.   Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication...
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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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DNA Replication02:40

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DNA replication involves the separation of the two strands of the double helix, with each strand serving as a template from which the new complementary strand is copied.  After replication, each double-stranded DNA includes one parental or “old” strand and one “new” strand. This is known as semiconservative replication. The resulting DNA molecules have the same sequence and are divided equally into the two daughter cells.
Replication in Prokaryotes
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Chromosome Replication02:31

Chromosome Replication

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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...
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Related Experiment Video

Updated: Jan 25, 2026

Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
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Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase

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Automated mapping of DNA replication fork progression in human cells with ForkML.

Victoria Rojat1, Diletta Ciardo1, Alan Tourancheau1

  • 1IBENS, Département de biologie, École Normale Supérieure, Université PSL, CNRS, INSERM, Paris, France.

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|January 23, 2026
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We developed ForkML, a new nanopore sequencing method to map DNA replication fork speed in the human genome. This technique accurately measures thousands of fork velocities, revealing slowdowns in transcribed genomic regions.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Biotechnology

Background:

  • Mapping DNA replication fork progression is crucial for understanding genome stability.
  • Existing methods for measuring fork speed have limitations in throughput and scalability.

Purpose of the Study:

  • To introduce ForkML, a high-throughput nanopore sequencing-based method for precise mapping of DNA replication fork velocities.
  • To analyze replication dynamics in relation to genomic and chromatin features.

Main Methods:

  • Utilizing nanopore sequencing technology.
  • Employing double pulse-labeling with BrdU incorporation in asynchronous cells.
  • Developing an automated computational pipeline for analyzing thousands of individual fork velocities.

Main Results:

  • ForkML accurately determines human fork speed, consistent with established data.
  • The method reliably detects replication stress.
  • ForkML reveals that replication forks slow down in early-replicating, transcribed genomic regions, linking replication dynamics to chromatin context.

Conclusions:

  • ForkML significantly enhances the throughput for measuring DNA replication fork progression.
  • The method provides novel insights into the relationship between replication dynamics, genomic features, and chromatin states.
  • ForkML is a powerful tool for studying genome replication and stability.