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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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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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Translesion DNA Polymerases02:10

Translesion DNA Polymerases

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Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
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The Replisome03:01

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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.
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Nucleosome Remodeling02:54

Nucleosome Remodeling

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Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
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Proofreading01:31

Proofreading

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Synthesis of new DNA molecules is carried out by the enzyme DNA polymerase, which adds nucleotides on the daughter strand complementary to the template DNA strand. DNA polymerase has a higher affinity to add the correct base and ensures fidelity during DNA replication. Furthermore,  it exhibits proofreading activity during replication, using an exonuclease domain that cuts off incorrect nucleotides from the nascent DNA strand.
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Updated: Sep 19, 2025

Plasmid-derived DNA Strand Displacement Gates for Implementing Chemical Reaction Networks
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Controlling DNA-RNA strand displacement kinetics with base distribution.

Eryk J Ratajczyk1,2,3, Jonathan Bath2,3, Petr Šulc4,5,6

  • 1Department of Physics, Rudolf Peierls Centre for Theoretical Physics, University of Oxford, Oxford OX1 3PU, United Kingdom.

Proceedings of the National Academy of Sciences of the United States of America
|June 6, 2025
PubMed
Summary
This summary is machine-generated.

DNA-RNA hybrid strand displacement is key for gene editing technologies like CRISPR-Cas9. Base distribution significantly impacts reaction speed, allowing for precise control over DNA-RNA interactions.

Keywords:
CRISPRDNA–RNA hybridscoarse-grained modelnucleic acidstrand displacement

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Area of Science:

  • Molecular Biology
  • Biophysics
  • Biochemistry

Background:

  • DNA-RNA hybrid strand displacement is fundamental to biological processes and synthetic systems.
  • Controlling these reactions is crucial for applications such as CRISPR-Cas9 gene editing.

Purpose of the Study:

  • To investigate the impact of base distribution on DNA-RNA strand displacement kinetics.
  • To compare sequence dependence in DNA-RNA hybrids versus all-DNA systems.
  • To validate computational models for predicting these reactions.

Main Methods:

  • Multiscale modeling combined with experimental strand displacement assays.
  • Characterization of reaction kinetics for RNA invasion of dsDNA and DNA invasion of hybrid duplexes.
  • Utilizing the oxNA coarse-grained model and developing a simple kinetic model.

Main Results:

  • Base distribution within the displacement domain strongly influences DNA-RNA reaction kinetics, unique to these hybrids.
  • Sequence-dependent reaction rates spanning over four orders of magnitude were achieved by redistributing bases.
  • All-DNA strand displacement showed predictable but weaker sequence dependence compared to DNA-RNA hybrids.
  • The oxNA model accurately reproduced experimental trends; a predictive kinetic model was developed.

Conclusions:

  • DNA-RNA strand displacement offers greater thermodynamic and kinetic control than all-DNA systems due to base distribution effects.
  • Base distribution may be a critical factor in natural R-loop formation and CRISPR guide RNA function.