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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-4763 | ||||||||||||||||||||||||
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Title | Cryo-EM structure of NCP_THF2(-1)-UV-DDB | ||||||||||||||||||||||||
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![]() | DNA damage / Nucleosome / THF2 photoproduct / DNA BINDING PROTEIN | ||||||||||||||||||||||||
Function / homology | ![]() positive regulation by virus of viral protein levels in host cell / epigenetic programming in the zygotic pronuclei / spindle assembly involved in female meiosis / Cul4-RING E3 ubiquitin ligase complex / UV-damage excision repair / biological process involved in interaction with symbiont / WD40-repeat domain binding / regulation of mitotic cell cycle phase transition / Cul4A-RING E3 ubiquitin ligase complex / Cul4B-RING E3 ubiquitin ligase complex ...positive regulation by virus of viral protein levels in host cell / epigenetic programming in the zygotic pronuclei / spindle assembly involved in female meiosis / Cul4-RING E3 ubiquitin ligase complex / UV-damage excision repair / biological process involved in interaction with symbiont / WD40-repeat domain binding / regulation of mitotic cell cycle phase transition / Cul4A-RING E3 ubiquitin ligase complex / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / negative regulation of reproductive process / negative regulation of developmental process / site of DNA damage / cullin family protein binding / viral release from host cell / negative regulation of tumor necrosis factor-mediated signaling pathway / pyrimidine dimer repair / negative regulation of megakaryocyte differentiation / ectopic germ cell programmed cell death / proteasomal protein catabolic process / positive regulation of viral genome replication / protein localization to CENP-A containing chromatin / protein autoubiquitination / Chromatin modifying enzymes / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / heterochromatin organization / epigenetic regulation of gene expression / Packaging Of Telomere Ends / response to UV / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Deposition of new CENPA-containing nucleosomes at the centromere / nucleosomal DNA binding / positive regulation of gluconeogenesis / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / Inhibition of DNA recombination at telomere / Meiotic synapsis / telomere organization / RNA Polymerase I Promoter Opening / Interleukin-7 signaling / Assembly of the ORC complex at the origin of replication / SUMOylation of chromatin organization proteins / DNA methylation / Condensation of Prophase Chromosomes / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / HCMV Late Events / innate immune response in mucosa / PRC2 methylates histones and DNA / Defective pyroptosis / HDACs deacetylate histones / nucleotide-excision repair / Recognition of DNA damage by PCNA-containing replication complex / RNA Polymerase I Promoter Escape / TP53 Regulates Transcription of DNA Repair Genes / lipopolysaccharide binding / Nonhomologous End-Joining (NHEJ) / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / DNA Damage Recognition in GG-NER / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / NoRC negatively regulates rRNA expression / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / B-WICH complex positively regulates rRNA expression / G2/M DNA damage checkpoint / HDMs demethylate histones / regulation of circadian rhythm / Dual Incision in GG-NER / DNA Damage/Telomere Stress Induced Senescence / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Metalloprotease DUBs / Formation of TC-NER Pre-Incision Complex / PKMTs methylate histone lysines / Meiotic recombination / RMTs methylate histone arginines / Wnt signaling pathway / Pre-NOTCH Transcription and Translation / Formation of Incision Complex in GG-NER / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / Transcriptional regulation of granulopoiesis / protein polyubiquitination / positive regulation of protein catabolic process / structural constituent of chromatin / antimicrobial humoral immune response mediated by antimicrobial peptide / UCH proteinases / cellular response to UV / nucleosome / rhythmic process / nucleosome assembly / E3 ubiquitin ligases ubiquitinate target proteins / cell junction / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / chromatin organization Similarity search - Function | ||||||||||||||||||||||||
Biological species | ![]() | ||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||||||||||||||||||||
![]() | Matsumoto S / Cavadini S | ||||||||||||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: DNA damage detection in nucleosomes involves DNA register shifting. 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 ...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 / ![]() ![]() 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. | ||||||||||||||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 76.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 29.5 KB 29.5 KB | Display Display | ![]() |
Images | ![]() | 146.9 KB | ||
Filedesc metadata | ![]() | 8.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 461.6 KB | Display | ![]() |
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Full document | ![]() | 461.2 KB | Display | |
Data in XML | ![]() | 6.5 KB | Display | |
Data in CIF | ![]() | 7.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6r8zMC ![]() 4762C ![]() 4764C ![]() 4765C ![]() 4766C ![]() 4767C ![]() 4768C ![]() 6r8yC ![]() 6r90C ![]() 6r91C ![]() 6r92C ![]() 6r93C ![]() 6r94C M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
+Entire : UV-DDB bound to a THF2 containing nucleosome
+Supramolecule #1: UV-DDB bound to a THF2 containing nucleosome
+Supramolecule #2: Histone H3.1, Histone H2A, Histone H2B
+Supramolecule #3: Histone H4
+Supramolecule #4: DNA
+Supramolecule #5: DNA damage-binding protein 1(2), DNA damage-binding protein 2
+Macromolecule #1: Histone H3.1
+Macromolecule #2: Histone H4
+Macromolecule #3: Histone H2A type 1-B/E
+Macromolecule #4: Histone H2B type 1-J
+Macromolecule #7: DNA damage-binding protein 1
+Macromolecule #8: DNA damage-binding protein 2
+Macromolecule #5: Human alpha-satellite DNA (145-MER)
+Macromolecule #6: Human alpha-satellite DNA (145-MER) with abasic sites at position...
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 2 mg/mL | ||||||||||||
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Buffer | pH: 7.4 Component:
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 85 % / Chamber temperature: 277 K / Instrument: LEICA EM GP |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Quantum LS / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Cs: 0.0 mm / Nominal magnification: 130000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 2) / Number images used: 129986 |
Initial angle assignment | Type: OTHER / Software - Name: RELION |
Final angle assignment | Type: OTHER / Software - Name: RELION |
-Atomic model buiding 1
Initial model |
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Refinement | Space: REAL / Protocol: FLEXIBLE FIT / Target criteria: Cross-correlation coefficient | ||||||||||||||||||||||||||
Output model | ![]() PDB-6r8z: |