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-Structure paper
Title | DNA damage detection in nucleosomes involves DNA register shifting. |
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Journal, issue, pages | Nature, Vol. 571, Issue 7763, Page 79-84, Year 2019 |
Publish date | May 29, 2019 |
Authors | Syota Matsumoto / Simone Cavadini / Richard D Bunker / Ralph S Grand / Alessandro Potenza / Julius Rabl / Junpei Yamamoto / Andreas D Schenk / Dirk Schübeler / Shigenori Iwai / Kaoru Sugasawa / Hitoshi Kurumizaka / Nicolas H Thomä / |
PubMed Abstract | Access to DNA packaged in nucleosomes is critical for gene regulation, DNA replication and DNA repair. In humans, the UV-damaged DNA-binding protein (UV-DDB) complex detects UV-light-induced ...Access to DNA packaged in nucleosomes is critical for gene regulation, DNA replication and DNA repair. In humans, the UV-damaged DNA-binding protein (UV-DDB) complex detects UV-light-induced pyrimidine dimers throughout the genome; however, it remains unknown how these lesions are recognized in chromatin, in which nucleosomes restrict access to DNA. Here we report cryo-electron microscopy structures of UV-DDB bound to nucleosomes bearing a 6-4 pyrimidine-pyrimidone dimer or a DNA-damage mimic in various positions. We find that UV-DDB binds UV-damaged nucleosomes at lesions located in the solvent-facing minor groove without affecting the overall nucleosome architecture. In the case of buried lesions that face the histone core, UV-DDB changes the predominant translational register of the nucleosome and selectively binds the lesion in an accessible, exposed position. Our findings explain how UV-DDB detects occluded lesions in strongly positioned nucleosomes, and identify slide-assisted site exposure as a mechanism by which high-affinity DNA-binding proteins can access otherwise occluded sites in nucleosomal DNA. |
External links | Nature / PubMed:31142837 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.5 - 4.8 Å |
Structure data | EMDB-4762, PDB-6r8y: EMDB-4763, PDB-6r8z: EMDB-4764, PDB-6r90: EMDB-4765, PDB-6r91: EMDB-4766, PDB-6r92: |
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Keywords | DNA BINDING PROTEIN / DNA damage / Nucleosome / 6-4 photoproduct / THF2 photoproduct / DNA |