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Related Concept Videos

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...
The Nucleosome Core Particle01:12

The Nucleosome Core Particle

Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
The Nucleosome Core Particle02:10

The Nucleosome Core Particle

Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
Spreading of Chromatin Modifications02:25

Spreading of Chromatin Modifications

The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...

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In Situ Nucleosome Assembly for Single-Molecule Correlative Force and Fluorescence Microscopy
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Nucleosome remodeling by hMSH2-hMSH6.

Sarah Javaid1, Mridula Manohar, Nidhi Punja

  • 1Department of Molecular Virology, Immunology, and Medical Genetics, Human Cancer Genetics, The Ohio State University and The Ohio State University Medical Center, Columbus, 43210, USA.

Molecular Cell
|January 13, 2010
PubMed
Summary

The mismatch repair complex hMSH2-hMSH6 disassembles nucleosomes by forming sliding clamps that translocate along DNA. Histone H3 acetylation enhances this process, supporting a passive chromatin remodeling mechanism.

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • DNA Repair

Background:

  • Chromatin, composed of DNA and proteins, is organized into nucleosomes, the fundamental units of DNA packaging.
  • DNA nucleotide mismatches and lesions pose threats to genomic integrity within chromatin.
  • The mismatch repair (MMR) system, including the hMSH2-hMSH6 heterodimer, is crucial for correcting these DNA errors.

Purpose of the Study:

  • To investigate the mechanism by which the hMSH2-hMSH6 complex interacts with and remodels nucleosomes.
  • To determine the role of histone modifications, specifically acetylation, in nucleosome disassembly by MMR proteins.
  • To elucidate the contribution of nucleosome structure to DNA mismatch recognition and repair.

Main Methods:

  • In vitro assays to study nucleosome disassembly by purified hMSH2-hMSH6 heterodimers.
  • Analysis of the effect of DNA mismatches on the formation and translocation of hMSH2-hMSH6 sliding clamps.
  • Biochemical experiments assessing the impact of histone H3 acetylation on DNA-octamer affinity and nucleosome stability.

Main Results:

  • The hMSH2-hMSH6 heterodimer disassembles nucleosomes in a process dependent on mismatch-induced sliding clamp formation.
  • Hydrolysis-independent hMSH2-hMSH6 sliding clamps translocate along DNA to the nucleosome, facilitating disassembly.
  • Histone H3 acetylation, particularly at the nucleosome entry-exit and dyad axis, enhances the rate of nucleosome disassembly by reducing DNA-octamer affinity.

Conclusions:

  • hMSH2-hMSH6 mediated nucleosome disassembly occurs via a passive chromatin remodeling mechanism involving sliding clamps trapping nucleosome fluctuations.
  • Histone H3 acetylation acts as a modulator, promoting MMR-associated chromatin remodeling.
  • These findings provide insights into the interplay between DNA repair, chromatin structure, and epigenetic modifications, supporting the Molecular Switch Model for MMR.