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Nucleosomes in solution exist as a mixture of twist-defect states
Rajeswari S Edayathumangalam1, Philipp Weyermann, Peter B Dervan
1Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523-1870, USA.
Journal of Molecular Biology
|November 30, 2004
Summary
A novel DNA clamp stabilizes nucleosomes by crossbracing the DNA superhelix. This study reveals twist-defect intermediates in nucleosomal DNA, impacting accessibility and chromatin remodeling.
Area of Science:
- Structural biology
- Molecular biology
- Biochemistry
Background:
- Nucleosomes are fundamental units of DNA packaging.
- Understanding nucleosome stability is crucial for DNA accessibility and gene regulation.
Purpose of the Study:
- To elucidate the structural mechanism of a pyrrole-imidazole polyamide clamp on nucleosomes.
- To investigate the dynamics and conformational states of nucleosomal DNA.
Main Methods:
- X-ray crystallography at 2.0 Å resolution.
- DNA footprinting techniques.
- Analysis of nucleosome conformations in solution and crystal structures.
Main Results:
- The bivalent polyamide clamp stabilizes nucleosomes by crossbracing the DNA superhelix.
- Nucleosomal DNA exists as a mixture of twist-defect intermediates in solution.
- Nucleosomes adopt distinct conformations, trapping these intermediates even with strong DNA sequences.
- Crystal structures reveal intermediates similar to those observed in solution.
Conclusions:
- The clamp effectively stabilizes nucleosomes against dissociation.
- Twist-defect states in nucleosomal DNA are prevalent and influence DNA accessibility.
- Twist diffusion is a significant mechanism for modulating nucleosomal DNA accessibility, potentially independent of ATP-dependent remodelers.