ArticleNature structural & molecular biology2021
BRCA1/BARD1 site-specific ubiquitylation of nucleosomal H2A is directed by BARD1.
Article in Nature structural & molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Mass Spectral Feature Analysis of Ubiquitylated Peptides Provides Insights into Probing the Dark Ubiquitylome.Journal of the American Society for Mass Spectrometry · 2024Pooled it
- Precision Chemistry for Protein Lysine Modification.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Review
- Proteome analyses reveal endoplasmic reticulum stress-induced changes in protein abundance associated with Ube2j2 deficiency in human cell culture.G3 (Bethesda, Md.) · 2026Article
- Mechanism of K63-linked polyubiquitin recognition and cleavage by the BRCA1-A complex.Nature communications · 2026Article
- Assessing the Clinical Relevance ofCurrent oncology (Toronto, Ont.) · 2026Article
- Small Structural Variations, Large Functional Consequences: Comparative Analysis Reveals Structural Control of Ubiquitylation Site Selection by BRCA1/BARD1.bioRxiv : the preprint server for biology · 2026Article
- The Landscape of BRCA1-Associated Post-Translational Modifications.Cell biology international · 2026Review
- g BRCA1 and g BRCA2 mutations in specific different domains affect ovarian cancer prognosis: A multicenter retrospective study.Chinese medical journal · 2026Article
- Structural basis for E4 enzyme Ufd2-catalyzed K48/K29 branched ubiquitin chains.Nature chemical biology · 2026Article
- Saturation genome editing ofmedRxiv : the preprint server for health sciences · 2025Article
- Structural insights into γH2Ax containing nucleosomes.Nucleic acids research · 2025Article
- Post-translational modification of H2B C-terminal helix regulates nucleosome interactions and chromatin signaling.Nucleic acids research · 2025Article
- PathogenicThe journal of physical chemistry. B · 2025Article
- Mechanism of nucleosomal H2A K13/15 monoubiquitination and adjacent dual monoubiquitination by RNF168.Nature chemical biology · 2025Article
- APC/C-mediated ubiquitylation of extranucleosomal histone complexes lacking canonical degrons.Nature communications · 2025Article
- 7-Dehydrocholesterol Reductase Activates the Hedgehog Pathway by Regulating Cholesterol to Promote the Development of Triple-Negative Breast Cancer.Current cancer drug targets · 2025Article
- The disordered negatively charged C-terminus of the large HECT E3 ubiquitin ligase HERC2 provides structural and thermal stability to the HECT C-lobe.Protein science : a publication of the Protein Society · 2024Article
- DOT1L-mediated RAP80 methylation promotes BRCA1 recruitment to elicit DNA repair.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- E3 ligases: a ubiquitous link between DNA repair, DNA replication and human disease.The Biochemical journal · 2024Review
- BRCA1/BARD1 ubiquitinates PCNA in unperturbed conditions to promote continuous DNA synthesis.Nature communications · 2024Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in the E3 ubiquitin ligase RING domains of BRCA1/BARD1 predispose carriers to breast and ovarian cancers. We present the structure of the BRCA1/BARD1 RING heterodimer with the E2 enzyme UbcH5c bound to its cellular target, the nucleosome, along with biochemical data that explain how the complex selectively ubiquitylates lysines 125, 127 and 129 in the flexible C-terminal tail of H2A in a fully human system. The structure reveals that a novel BARD1-histone interface couples to a repositioning of UbcH5c compared to the structurally similar PRC1 E3 ligase Ring1b/Bmi1 that ubiquitylates H2A Lys119 in nucleosomes. This interface is sensitive to both H3 Lys79 methylation status and mutations found in individuals with cancer. Furthermore, NMR reveals an unexpected mode of E3-mediated substrate regulation through modulation of dynamics in the C-terminal tail of H2A. Our findings provide insight into how E3 ligases preferentially target nearby lysine residues in nucleosomes by a steric occlusion and distancing mechanism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.