|Title||DNA damage detection in nucleosomes involves DNA register shifting.|
|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||PubMed:31142837 / Publisher's page|
|Keywords||Cryoelectron Microscopy / DDB1 protein, human / DDB2 protein, human / DNA / DNA Damage / DNA-Binding Proteins / Histones / Humans / Models, Molecular / Nucleosomes / Pyrimidine Dimers / Thermodynamics / Ultraviolet Rays / pyrimidine-pyrimidone dimer / DNA BINDING PROTEIN / Nucleosome / 6-4 photoproduct / THF2 photoproduct|
|Methods||EM (single particle)|
|Resolution||3.5 - 4.8 A|
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