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Mismatch Repair

Mismatch Repair

Mismatch Repair

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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.
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Huntington Disease l: Introduction

Huntington Disease l: Introduction

Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...

Homologous Recombination

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...

Base Excision Repair

Base Excision Repair

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.
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Related Experiment Video

Updated: Jul 13, 2026

Using Next Generation Sequencing to Identify Mutations Associated with Repair of a CAS9-induced Double Strand Break Near the CD4 Promoter

Using Next Generation Sequencing to Identify Mutations Associated with Repair of a CAS9-induced Double Strand Break Near the CD4 Promoter

Published on: March 31, 2022

Targeting DNA mismatch repair in Huntington's disease.

Emma L Bunting¹, Amol Panhale², Peter McColgan¹

¹Roche Products Ltd, Welwyn Garden City, UK.

Trends in Neurosciences

|July 11, 2026

Summary

This summary is machine-generated.

Huntington's disease (HD) involves harmful HTT CAG repeat expansion, driven by DNA repair errors. Targeting mismatch repair (MMR) proteins may slow this expansion, offering a potential therapeutic strategy for HD.

Keywords:

genetic modifiers microsatellite instability polyposis somatic expansion therapeutic targets transcriptionopathy

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

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Published on: June 19, 2018

Area of Science:

Neuroscience
Genetics
Molecular Biology

Background:

Huntington's disease (HD) pathogenesis is characterized by somatic expansion of the HTT CAG repeat.
Mismatch repair (MMR) enzymes are implicated in driving this expansion through erroneous DNA repair.
Genetic variations in MMR genes influence HD onset and progression.

Purpose of the Study:

To synthesize current knowledge on CAG repeat-length-dependent changes in HD.
To evaluate key MMR proteins (MSH3, MLH3, PMS1) as therapeutic targets.
To outline safety considerations for MMR-modulating therapies.

Main Methods:

Review of post-mortem brain tissue studies.
Analysis of cell system data.
Examination of findings from mouse models of HD.

Main Results:

Confirmed elevated somatic expansion in medium spiny neurons, linked to HD vulnerability.
Identified specific CAG repeat expansion thresholds associated with cellular pathogenesis stages.
Detailed CAG repeat-length-dependent molecular and cellular alterations.

Conclusions:

Somatic expansion of the HTT CAG repeat is a critical factor in HD.
MSH3, MLH3, and PMS1 are promising therapeutic targets for reducing somatic expansion.
Careful consideration of safety is essential for MMR-modulating therapeutic approaches in HD.