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Related Concept Videos

Lagging Strand Synthesis01:59

Lagging Strand Synthesis

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During replication, the complementary strands in double-stranded DNA are synthesized at different rates. Replication first begins on the leading strand. Replication starts later, occurs more slowly, and proceeds discontinuously on the lagging strand.
There are several major differences between synthesis of the leading strand and synthesis of the lagging strand. 1) Leading strand synthesis happens in the direction of replication fork opening, whereas lagging strand synthesis happens in the...
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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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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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The Replisome03:01

The Replisome

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DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...
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DNA Replication02:40

DNA Replication

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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
DNA replication...
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Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

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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: May 25, 2025

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

Published on: May 2, 2025

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Supervised and unsupervised deep learning-based approaches for studying DNA replication spatiotemporal dynamics.

Julian Ng-Kee-Kwong1, Ben Philps2, Fiona N C Smith2

  • 1Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Roger Land Building, Alexander Crum Brown Road, Edinburgh, EH9 3FF, UK.

Communications Biology
|February 26, 2025
PubMed
Summary
This summary is machine-generated.

Researchers developed new machine learning methods to efficiently detect aberrant DNA replication in cells. This advance aids in understanding DNA replication

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Area of Science:

  • Cell Biology
  • Genetics
  • Bioinformatics

Background:

  • DNA replication is crucial for cell division and is tightly regulated spatially and temporally in eukaryotic cells.
  • Aberrant DNA replication is linked to various human diseases, but studying it is challenging due to labor-intensive methods.
  • Existing methods hinder large-scale analyses of DNA replication's role in pathology.

Purpose of the Study:

  • To develop novel, efficient computational methods for analyzing DNA replication dynamics.
  • To identify altered replication patterns in disease-associated genetic contexts.
  • To enable large-scale detection of aberrant S-phase cells for pathological studies.

Main Methods:

  • Applied supervised machine learning to classify S-phase patterns in mouse embryonic stem cells (mESCs).
  • Developed an unsupervised machine learning method for large-scale detection of aberrant S-phase cells.
  • Validated the unsupervised method using a cellular model of deregulated origin firing (cyclin E overexpression).
  • Utilized EdU and PCNA-based analyses for method validation.

Main Results:

  • Successfully classified S-phase patterns in wild-type mESCs using supervised learning.
  • Identified altered replication dynamics in Rif1-deficient mESCs.
  • The unsupervised method autonomously detected expected genotypic differences in replication.
  • Demonstrated the method's applicability to patient samples.

Conclusions:

  • Novel machine learning approaches significantly improve the analysis of DNA replication.
  • The unsupervised method offers a scalable solution for detecting aberrant S-phase cells.
  • This technology can help elucidate the contribution of deregulated DNA replication to human diseases.
  • Potential for application in clinical settings for patient sample analysis.