ArticleNucleic acids research2023
Structure and functional determinants of Rad6-Bre1 subunits in the histone H2B ubiquitin-conjugating complex.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Histone H2B monoubiquitination drives sexual commitment in malaria parasites.Nature microbiology · 2026Article
- FgNup2 regulates nuclear import of the histone H2B monoubiquitination enzyme by stabilizing the FgImpα-FgBre1 complex to mediate pathogenicity in Fusarium graminearum.PLoS pathogens · 2026Article
- Structural insights into the Bre1-Lge1 and RNF20/RNF40-WAC interactions critical for H2B ubiquitination.Nucleic acids research · 2026Article
- The Lysine Deprotonation Mechanism in a Ubiquitin Conjugating Enzyme.The journal of physical chemistry. B · 2025Article
- In silico identification of novel natural compounds as potential KIFC1 inhibitors for the therapeutic intervention of triple-negative breast cancer.Frontiers in bioinformatics · 2025Article
- Testis-specific H2B.W1 disrupts nucleosome integrity by reducing DNA-histone interactions.Nucleic acids research · 2024Article
- Histone H2B ubiquitylation: Connections to transcription and effects on chromatin structure.Biochimica et biophysica acta. Gene regulatory mechanisms · 2024Review
- UBE2A and UBE2B are recruited by an atypical E3 ligase module in UBR4.Nature structural & molecular biology · 2024Article
- Mechanism of histone H2B monoubiquitination by Bre1.Nature structural & molecular biology · 2023Article
- Structure-function analysis of histone H2B and PCNA ubiquitination dynamics using deubiquitinase-deficient strains.Scientific reports · 2023Article
- Rapid purification of rabbit immunoglobulins using a single-step, negative-selection chromatography.Protein expression and purification · 2023Article
- Paf1 complex subunit Rtf1 stimulates H2B ubiquitylation by interacting with the highly conserved N-terminal helix of Rad6.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
The conserved complex of the Rad6 E2 ubiquitin-conjugating enzyme and the Bre1 E3 ubiquitin ligase catalyzes histone H2B monoubiquitination (H2Bub1), which regulates chromatin dynamics during transcription and other nuclear processes. Here, we report a crystal structure of Rad6 and the non-RING domain N-terminal region of Bre1, which shows an asymmetric homodimer of Bre1 contacting a conserved loop on the Rad6 'backside'. This contact is distant from the Rad6 catalytic site and is the location of mutations that impair telomeric silencing in yeast. Mutational analyses validated the importance of this contact for the Rad6-Bre1 interaction, chromatin-binding dynamics, H2Bub1 formation and gene expression. Moreover, the non-RING N-terminal region of Bre1 is sufficient to confer nucleosome binding ability to Rad6 in vitro. Interestingly, Rad6 P43L protein, an interaction interface mutant and equivalent to a cancer mutation in the human homolog, bound Bre1 5-fold more tightly than native Rad6 in vitro, but showed reduced chromatin association of Bre1 and reduced levels of H2Bub1 in vivo. These surprising observations imply conformational transitions of the Rad6-Bre1 complex during its chromatin-associated functional cycle, and reveal the differential effects of specific disease-relevant mutations on the chromatin-bound and unbound states. Overall, our study provides structural insights into Rad6-Bre1 interaction through a novel interface that is important for their biochemical and biological responses.
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