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Related Concept Videos

Huntington Disease l: Introduction01:21

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,...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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...
Translesion DNA Polymerases02:10

Translesion DNA Polymerases

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.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

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...

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Related Experiment Video

Updated: Jun 25, 2026

Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System
10:52

Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System

Published on: December 10, 2021

DNA instability in replicating Huntington's disease lymphoblasts.

Milena Cannella1, Vittorio Maglione, Tiziana Martino

  • 1Neurogenetics Unit, IRCCS Neuromed, Pozzilli, IS, Italy. genetics@neuromed.it

BMC Medical Genetics
|February 13, 2009
PubMed
Summary

Huntington's disease (HD) CAG repeat length significantly influences somatic variation, with larger expansions showing greater instability. Certain drugs can control this triplet expansion in HD cell lines.

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Related Experiment Videos

Last Updated: Jun 25, 2026

Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System
10:52

Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System

Published on: December 10, 2021

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
07:08

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Published on: February 27, 2018

Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells
11:06

Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells

Published on: February 24, 2014

Area of Science:

  • Genetics
  • Molecular Biology
  • Neurodegenerative Diseases

Background:

  • Huntington's disease (HD) is characterized by expanded CAG repeats in the HD gene.
  • Tissue-specific variability in repeat length (triplet mosaicism) occurs in both mitotic and postmitotic cells.
  • The underlying mechanisms of CAG repeat mutability in HD remain largely unknown.

Purpose of the Study:

  • To investigate environmental and genetic factors influencing CAG repeat mutability in HD.
  • To explore the role of cell replication in determining CAG repeat instability.
  • To utilize cultured HD patient lymphoblasts as a model system.

Main Methods:

  • Cultured lymphoblasts from HD patients with varying CAG repeat lengths were used.
  • Cell lines were cultured for extended periods (six months or more).
  • The impact of certain drugs on triplet expansion was assessed in prone-to-expand HD cell lines.

Main Results:

  • Most cell lines (88%) exhibited minimal repeat instability.
  • Lymphoblasts with large CAG repeat expansions (>60 repeats) showed increased mutation size and triplet mosaicism during replication.
  • No significant influence of investigated genetic factors acting in cis was observed.
  • Specific drugs demonstrated control over triplet expansion in susceptible HD cell lines.

Conclusions:

  • Inherited CAG repeat length is a major determinant of somatic repeat variation in HD.
  • Larger triplet expansions exhibit significant somatic variations.
  • These findings provide a model for studying drug-controlled triplet instability and associated genetic factors in HD.