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Related Concept Videos

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...
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
Base Excision Repair01:54

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.
The first step of...
Base Excision Repair01:54

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.
The first step of...
Nucleosome Remodeling02:54

Nucleosome Remodeling

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
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...

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Preparation of Nucleosome Core Particles Complexed with DNA Repair Factors for Cryo-Electron Microscopy Structural Determination
07:59

Preparation of Nucleosome Core Particles Complexed with DNA Repair Factors for Cryo-Electron Microscopy Structural Determination

Published on: August 17, 2022

Chromatin modifications and nucleotide excision repair.

Raymond Waters1, Simon H Reed, Yachuan Yu

  • 1Pathology Department, Cardiff University, School of Medicine, Heath Park, Cardiff.

SEB Experimental Biology Series
|March 29, 2008
PubMed
Summary

Researchers developed a new method to study DNA repair rates in yeast, revealing how UV radiation affects DNA lesions and chromatin structure. This work highlights the roles of histone acetylation and chromatin remodeling in DNA repair processes.

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Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • UV radiation causes DNA damage, primarily cyclobutane pyrimidine dimers.
  • DNA repair mechanisms, including nucleotide excision repair (NER), are crucial for maintaining genomic integrity.
  • Chromatin structure, including nucleosome positioning and modifications, influences DNA accessibility and repair.

Purpose of the Study:

  • To develop and apply a novel method for analyzing DNA repair at nucleotide resolution in yeast.
  • To investigate the impact of UV-induced DNA damage on nucleosome modification and chromatin remodeling.
  • To elucidate the roles of specific proteins, such as Gcn5 and Swi2, in DNA repair and chromatin dynamics.

Main Methods:

  • Development of a nucleotide-resolution technique to quantify DNA repair events.
  • Utilizing the MFA2 gene in yeast as a model system.
  • Assessing histone acetylation (H3) and chromatin accessibility changes post-UV exposure.
  • Investigating the involvement of Gcn5 histone acetyltransferase and Swi2 (a SWI/SNF factor).

Main Results:

  • Determined sequence-specific DNA repair rates for individual UV-induced lesions.
  • Observed UV-induced histone acetylation, primarily at H3, mediated by Gcn5, which is essential for efficient repair.
  • Demonstrated UV-triggered chromatin remodeling, evidenced by increased accessibility of nucleosomal DNA, partly mediated by Swi2.
  • Found that histone acetylation and chromatin remodeling occur independently of functional NER.

Conclusions:

  • The developed method allows precise measurement of DNA repair rates and chromatin changes.
  • Histone acetylation and chromatin remodeling are early responses to UV damage that facilitate DNA repair.
  • NER is required for the restoration of the pre-UV chromatin state, but not for the initial damage response and repair facilitation.