6R8Z
Cryo-EM structure of NCP_THF2(-1)-UV-DDB
Summary for 6R8Z
| Entry DOI | 10.2210/pdb6r8z/pdb |
| EMDB information | 4763 |
| Descriptor | Histone H3.1, Histone H4, Histone H2A type 1-B/E, ... (8 entities in total) |
| Functional Keywords | dna damage, nucleosome, thf2 photoproduct, dna binding protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 12 |
| Total formula weight | 379368.66 |
| Authors | Matsumoto, S.,Cavadini, S.,Bunker, R.D.,Thoma, N.H. (deposition date: 2019-04-02, release date: 2019-06-12, Last modification date: 2024-05-22) |
| Primary citation | Matsumoto, S.,Cavadini, S.,Bunker, R.D.,Grand, R.S.,Potenza, A.,Rabl, J.,Yamamoto, J.,Schenk, A.D.,Schubeler, D.,Iwai, S.,Sugasawa, K.,Kurumizaka, H.,Thoma, N.H. DNA damage detection in nucleosomes involves DNA register shifting. Nature, 571:79-84, 2019 Cited by 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 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. PubMed: 31142837DOI: 10.1038/s41586-019-1259-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.9 Å) |
Structure validation
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