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- PDB-7e8i: Structural insight into BRCA1-BARD1 complex recruitment to damage... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7e8i | |||||||||||||||||||||||||||
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Title | Structural insight into BRCA1-BARD1 complex recruitment to damaged chromatin | |||||||||||||||||||||||||||
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![]() | NUCLEAR PROTEIN / BRCA1 / nucleosome / DNA damage / chromatin / BARD1 | |||||||||||||||||||||||||||
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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||||||||||||||||||||
![]() | Dai, Y. / Dai, L. / Zhou, Z. | |||||||||||||||||||||||||||
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
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 355.9 KB | Display | ![]() |
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PDB format | ![]() | 271 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 944.8 KB | Display | ![]() |
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Full document | ![]() | 962.5 KB | Display | |
Data in XML | ![]() | 39.7 KB | Display | |
Data in CIF | ![]() | 62.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 31020MC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-DNA chain , 2 types, 2 molecules JI
#1: DNA chain | Mass: 44992.648 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: DNA chain | Mass: 44521.367 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Protein , 6 types, 10 molecules AEBFCGDHKL
#3: Protein | Mass: 15303.930 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #4: Protein | Mass: 11263.231 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #5: Protein | Mass: 13952.205 Da / Num. of mol.: 2 / Mutation: K16C Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Gene: h2ac14.L, h2ac14, hist1h2aj, LOC494591, XELAEV_18003602mg Production host: ![]() ![]() #6: Protein | Mass: 13524.752 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #7: Protein | | Mass: 40145.836 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: Q99728, RING-type E3 ubiquitin transferase #8: Protein | | Mass: 9755.145 Da / Num. of mol.: 1 / Mutation: G76C Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 168313 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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