8OFF
Structure of BARD1 ARD-BRCTs in complex with H2AKc15ub nucleosomes (Map1)
This is a non-PDB format compatible entry.
Summary for 8OFF
| Entry DOI | 10.2210/pdb8off/pdb |
| Related | 8OFF |
| EMDB information | 16859 17928 |
| Descriptor | DNA (142-MER), Histone H3.1, Histone H2B type 1-C/E/F/G/I, ... (7 entities in total) |
| Functional Keywords | brca1-bard1, chromatin recognition, nucleosomes, ubiquitin, dna binding protein |
| Biological source | Homo sapiens More |
| Total number of polymer chains | 13 |
| Total formula weight | 506205.59 |
| Authors | Foglizzo, M.,Burdett, H.,Wilson, M.D.,Zeqiraj, E. (deposition date: 2023-03-15, release date: 2023-10-11, Last modification date: 2023-11-22) |
| Primary citation | Burdett, H.,Foglizzo, M.,Musgrove, L.J.,Kumar, D.,Clifford, G.,Campbell, L.J.,Heath, G.R.,Zeqiraj, E.,Wilson, M.D. BRCA1-BARD1 combines multiple chromatin recognition modules to bridge nascent nucleosomes. Nucleic Acids Res., 51:11080-11103, 2023 Cited by PubMed Abstract: Chromatin association of the BRCA1-BARD1 heterodimer is critical to promote homologous recombination repair of DNA double-strand breaks (DSBs) in S/G2. How the BRCA1-BARD1 complex interacts with chromatin that contains both damage induced histone H2A ubiquitin and inhibitory H4K20 methylation is not fully understood. We characterised BRCA1-BARD1 binding and enzymatic activity to an array of mono- and di-nucleosome substrates using biochemical, structural and single molecule imaging approaches. We found that the BRCA1-BARD1 complex preferentially interacts and modifies di-nucleosomes over mono-nucleosomes, allowing integration of H2A Lys-15 ubiquitylation signals with other chromatin modifications and features. Using high speed- atomic force microscopy (HS-AFM) to monitor how the BRCA1-BARD1 complex recognises chromatin in real time, we saw a highly dynamic complex that bridges two nucleosomes and associates with the DNA linker region. Bridging is aided by multivalent cross-nucleosome interactions that enhance BRCA1-BARD1 E3 ubiquitin ligase catalytic activity. Multivalent interactions across nucleosomes explain how BRCA1-BARD1 can recognise chromatin that retains partial di-methylation at H4 Lys-20 (H4K20me2), a parental histone mark that blocks BRCA1-BARD1 interaction with nucleosomes, to promote its enzymatic and DNA repair activities. PubMed: 37823591DOI: 10.1093/nar/gkad793 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.4 Å) |
Structure validation
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