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- EMDB-31020: Structural insight into BRCA1-BARD1 complex recruitment to damage... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-31020 | |||||||||||||||||||||||||||
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Title | Structural insight into BRCA1-BARD1 complex recruitment to damaged chromatin | |||||||||||||||||||||||||||
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![]() | BRCA1 / nucleosome / DNA damage / chromatin / BARD1 / NUCLEAR PROTEIN | |||||||||||||||||||||||||||
Function / homology | ![]() negative regulation of mRNA 3'-end processing / Defective DNA double strand break response due to BRCA1 loss of function / Defective DNA double strand break response due to BARD1 loss of function / BRCA1-BARD1 complex / BRCA1-C complex / BRCA1-B complex / BRCA1-A complex / nuclear ubiquitin ligase complex / DNA strand resection involved in replication fork processing / homologous recombination ...negative regulation of mRNA 3'-end processing / Defective DNA double strand break response due to BRCA1 loss of function / Defective DNA double strand break response due to BARD1 loss of function / BRCA1-BARD1 complex / BRCA1-C complex / BRCA1-B complex / BRCA1-A complex / nuclear ubiquitin ligase complex / DNA strand resection involved in replication fork processing / homologous recombination / tissue homeostasis / protein K6-linked ubiquitination / regulation of DNA damage checkpoint / regulation of phosphorylation / Impaired BRCA2 binding to PALB2 / mitotic G2/M transition checkpoint / negative regulation of protein export from nucleus / Defective homologous recombination repair (HRR) due to BRCA1 loss of function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function / Homologous DNA Pairing and Strand Exchange / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / Resolution of D-loop Structures through Holliday Junction Intermediates / HDR through Single Strand Annealing (SSA) / Impaired BRCA2 binding to RAD51 / Presynaptic phase of homologous DNA pairing and strand exchange / negative regulation of cell cycle / regulation of DNA repair / ubiquitin ligase complex / cellular response to ionizing radiation / Nonhomologous End-Joining (NHEJ) / RING-type E3 ubiquitin transferase / G2/M DNA damage checkpoint / HDR through Homologous Recombination (HRR) / Metalloprotease DUBs / kinase binding / cytoplasmic ribonucleoprotein granule / modification-dependent protein catabolic process / positive regulation of protein catabolic process / structural constituent of chromatin / ubiquitin-protein transferase activity / protein tag activity / UCH proteinases / nucleosome / nucleosome assembly / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / Processing of DNA double-strand break ends / Regulation of TP53 Activity through Phosphorylation / regulation of cell cycle / protein ubiquitination / nuclear speck / positive regulation of apoptotic process / protein heterodimerization activity / DNA repair / ubiquitin protein ligase binding / DNA damage response / negative regulation of apoptotic process / protein homodimerization activity / DNA binding / RNA binding / nucleoplasm / nucleus / metal ion binding / cytoplasm Similarity search - Function | |||||||||||||||||||||||||||
Biological species | ![]() ![]() | |||||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||||||||||||||||||||
![]() | Dai Y / Dai L | |||||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural insight into BRCA1-BARD1 complex recruitment to damaged chromatin. Authors: Linchang Dai / Yaxin Dai / Jinhua Han / Yan Huang / Longge Wang / Jun Huang / Zheng Zhou / ![]() Abstract: The BRCA1-BARD1 complex directs the DNA double-strand break (DSB) repair pathway choice to error-free homologous recombination (HR) during the S-G2 stages. Targeting BRCA1-BARD1 to DSB-proximal sites ...The BRCA1-BARD1 complex directs the DNA double-strand break (DSB) repair pathway choice to error-free homologous recombination (HR) during the S-G2 stages. Targeting BRCA1-BARD1 to DSB-proximal sites requires BARD1-mediated nucleosome interaction and histone mark recognition. Here, we report the cryo-EM structure of BARD1 bound to a ubiquitinated nucleosome core particle (NCP) at 3.1 Å resolution and illustrate how BARD1 simultaneously recognizes the DNA damage-induced mark H2AK15ub and DNA replication-associated mark H4K20me0 on the nucleosome. In vitro and in vivo analyses reveal that the BARD1-NCP complex is stabilized by BARD1-nucleosome interaction, BARD1-ubiquitin interaction, and BARD1 ARD domain-BARD1 BRCT domain interaction, and abrogating these interactions is detrimental to HR activity. We further identify multiple disease-causing BARD1 mutations that disrupt BARD1-NCP interactions and hence impair HR. Together, this study elucidates the mechanism of BRCA1-BARD1 complex recruitment and retention by DSB-flanking nucleosomes and sheds important light on cancer therapeutic avenues. | |||||||||||||||||||||||||||
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 | ![]() | 59.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21 KB 21 KB | Display Display | ![]() |
Images | ![]() | 47.9 KB | ||
Filedesc metadata | ![]() | 6.2 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 502.3 KB | Display | ![]() |
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Full document | ![]() | 501.8 KB | Display | |
Data in XML | ![]() | 5.4 KB | Display | |
Data in CIF | ![]() | 6.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7e8iMC 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
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 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 : BARD1-NCP-Ubiquitin complex
+Supramolecule #1: BARD1-NCP-Ubiquitin complex
+Supramolecule #2: DNA
+Supramolecule #3: Histone
+Supramolecule #4: BARD1-Ubiquitin
+Macromolecule #1: DNA (145-MER)
+Macromolecule #2: DNA (145-MER)
+Macromolecule #3: Histone H3
+Macromolecule #4: Histone H4
+Macromolecule #5: Histone H2A
+Macromolecule #6: Histone H2B 1.1
+Macromolecule #7: BRCA1-associated RING domain protein 1
+Macromolecule #8: Polyubiquitin-B
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: PDB ENTRY |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 168313 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |