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Related Concept Videos

Mismatch Repair01:20

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
Mismatch Repair01:36

Mismatch Repair

Overview
Mismatch Repair01:36

Mismatch Repair

Overview
Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

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, a...
Gene Conversion02:08

Gene Conversion

Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...

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Related Experiment Video

Updated: May 27, 2026

Application of Stopped-flow Kinetics Methods to Investigate the Mechanism of Action of a DNA Repair Protein
11:01

Application of Stopped-flow Kinetics Methods to Investigate the Mechanism of Action of a DNA Repair Protein

Published on: March 31, 2010

Base-flipping mechanism in postmismatch recognition by MutS.

Sean M Law1, Michael Feig

  • 1Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, Michigan, USA.

Biophysical Journal
|November 10, 2011
PubMed
Summary

DNA mismatch repair protein MutS recognizes genome errors. Simulations reveal DNA base flipping during repair initiation, suggesting a role in forming repair complexes.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • DNA mismatch recognition and repair are crucial for maintaining genome stability.
  • The MutS protein is conserved across species and plays a key role in identifying DNA mismatches.
  • Understanding the molecular mechanisms of mismatch recognition is essential for comprehending DNA repair pathways.

Purpose of the Study:

  • To investigate the conformational dynamics of DNA surrounding a G·T mismatch during MutS binding.
  • To elucidate the energetics and structural changes associated with DNA base flipping in the MutS-DNA complex.
  • To explore the potential role of base flipping in the initiation of DNA repair.

Main Methods:

  • Molecular dynamics (MD) simulations of the Escherichia coli MutS-DNA complex.

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Last Updated: May 27, 2026

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  • Hamiltonian replica exchange free energy calculations to determine base flipping energetics.
  • Analysis of structural changes in both DNA and MutS during the simulated process.

    • Main Results:

    • Significant DNA conformational dynamics were observed around the G·T mismatch, including weakened hydrogen bonding and base opening.
    • A stable base-flipped-out state was identified with a low initial energy barrier of approximately 2 kcal/mol.
    • Correlations between DNA/MutS structural changes and base flipping were detected, suggesting a dynamic interaction.

    Conclusions:

    • DNA base flipping is a key dynamic event during MutS-mediated mismatch recognition.
    • Base flipping may serve as an early step in initiating DNA repair, potentially leading to sliding-clamp formation.
    • These findings provide insights into the mechanistic details of DNA repair initiation.