Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Mismatch Repair01:36

Mismatch Repair

43.7K
Overview
43.7K
Mismatch Repair01:20

Mismatch Repair

6.6K
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...
6.6K
Overview of DNA Repair02:25

Overview of DNA Repair

33.8K
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
33.8K
Base Excision Repair01:54

Base Excision Repair

26.4K
One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
26.4K
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

40.9K
Overview
40.9K
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

5.2K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
5.2K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Comparative Analysis of Ultra-Low Versus Hydrogel Growing Conditions for Patient-Derived Glioma Organoids.

Frontiers in bioscience (Landmark edition)·2026
Same author

Mechanism of MutLβ-dependent DNA expansions.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same author

Biomarkers.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2025
Same author

Dynamics of endemic virus re-emergence in children in the USA following the COVID-19 pandemic (2022-23): a prospective, multicentre, longitudinal, immunoepidemiological surveillance study.

The Lancet. Infectious diseases·2025
Same author

Evaluation of Clastogenic and Aneugenic Action of Two Bio-Insecticides Using Allium Bioassay.

Journal of xenobiotics·2025
Same author

Potential of Newly Synthesized Sea Buckthorn Phytocarriers as Anti-Inflammatory Active Agents.

Pharmaceuticals (Basel, Switzerland)·2025

Related Experiment Video

Updated: Feb 8, 2026

Proofreading and DNA Repair Assay Using Single Nucleotide Extension and MALDI-TOF Mass Spectrometry Analysis
11:08

Proofreading and DNA Repair Assay Using Single Nucleotide Extension and MALDI-TOF Mass Spectrometry Analysis

Published on: June 19, 2018

10.2K

Endonucleolytic function of MutLalpha in human mismatch repair.

Farid A Kadyrov1, Leonid Dzantiev, Nicoleta Constantin

  • 1Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.

Cell
|July 29, 2006
PubMed
Summary
This summary is machine-generated.

Human MutLalpha (MLH1*PMS2) acts as a latent endonuclease in DNA mismatch repair. It becomes active with other proteins to initiate DNA excision, crucial for hereditary nonpolyposis colon cancer.

More Related Videos

A Standard Methodology to Examine On-site Mutagenicity As a Function of Point Mutation Repair Catalyzed by CRISPR/Cas9 and SsODN in Human Cells
10:07

A Standard Methodology to Examine On-site Mutagenicity As a Function of Point Mutation Repair Catalyzed by CRISPR/Cas9 and SsODN in Human Cells

Published on: August 25, 2017

8.5K
Imaging Mismatch Repair and Cellular Responses to DNA Damage in Bacillus subtilis
10:28

Imaging Mismatch Repair and Cellular Responses to DNA Damage in Bacillus subtilis

Published on: February 9, 2010

11.8K

Related Experiment Videos

Last Updated: Feb 8, 2026

Proofreading and DNA Repair Assay Using Single Nucleotide Extension and MALDI-TOF Mass Spectrometry Analysis
11:08

Proofreading and DNA Repair Assay Using Single Nucleotide Extension and MALDI-TOF Mass Spectrometry Analysis

Published on: June 19, 2018

10.2K
A Standard Methodology to Examine On-site Mutagenicity As a Function of Point Mutation Repair Catalyzed by CRISPR/Cas9 and SsODN in Human Cells
10:07

A Standard Methodology to Examine On-site Mutagenicity As a Function of Point Mutation Repair Catalyzed by CRISPR/Cas9 and SsODN in Human Cells

Published on: August 25, 2017

8.5K
Imaging Mismatch Repair and Cellular Responses to DNA Damage in Bacillus subtilis
10:28

Imaging Mismatch Repair and Cellular Responses to DNA Damage in Bacillus subtilis

Published on: February 9, 2010

11.8K

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Hereditary nonpolyposis colon cancer (HNPCC) is linked to mutations in MutLalpha (MLH1*PMS2).
  • MutLalpha's precise role in DNA mismatch repair remains incompletely understood.

Purpose of the Study:

  • To elucidate the function of human MutLalpha in DNA mismatch repair.
  • To identify the mechanism by which MutLalpha initiates DNA excision during mismatch repair.

Main Methods:

  • In vitro biochemical assays using purified proteins (MutLalpha, MutSalpha, RFC, PCNA) and DNA substrates.
  • Site-directed mutagenesis to investigate the endonuclease active site.
  • Comparative analysis of PMS2 homologs and bacterial MutL proteins.

Main Results:

  • Human MutLalpha functions as a latent endonuclease, activated by a complex of mismatch, MutSalpha, RFC, PCNA, and ATP.
  • The MutLalpha-containing system incises DNA heteroduplexes at a nicked strand near a mismatch.
  • Exonuclease I, activated by MutSalpha, removes the mismatch-containing DNA segment.
  • A conserved PMS2 motif (DQHA(X)(2)E(X)(4)E) is likely the endonuclease active site.

Conclusions:

  • MutLalpha's endonuclease activity is critical for initiating DNA excision in mismatch repair.
  • The identified active site motif suggests evolutionary conservation and potential differences in mismatch repair mechanisms across species.
  • Understanding MutLalpha's function provides insights into HNPCC pathogenesis.