Evidence map›Paper›PMID 36715322›Full record

ArticleNucleic acids research2023

Structure and functional determinants of Rad6-Bre1 subunits in the histone H2B ubiquitin-conjugating complex.

Prakash K Shukla, Jesse E Bissell, Sanjit Kumar, Srijana Pokhrel, Sowmiya Palani, Kaitlin S Radmall, Onyeka Obidi, Timothy J Parnell, Julia Brasch, Dennis C Shrieve and 1 more

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Histone H2B ubiquitylation: Connections to transcription and effects on chromatin structure.Biochimica et biophysica acta. Gene regulatory mechanisms · 2024
    Review
  8. Article
  9. Mechanism of histone H2B monoubiquitination by Bre1.Nature structural & molecular biology · 2023
    Article
  10. Article
  11. Article
  12. 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 · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 2 countries.

Prakash K ShuklaDepartment of Radiation Oncology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Jesse E BissellDepartment of Radiation Oncology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Sanjit KumarCentre for Bioseparation Technology, Vellore Institute of Technology, Vellore, Tamil Nadu 632014, India.
Srijana PokhrelDepartment of Radiation Oncology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Sowmiya PalaniDepartment of Radiation Oncology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Kaitlin S RadmallDepartment of Radiation Oncology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Onyeka ObidiDepartment of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Timothy J ParnellHuntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Julia BraschDepartment of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Dennis C ShrieveDepartment of Radiation Oncology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Mahesh B ChandrasekharanDepartment of Radiation Oncology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.ORCID 0000-0002-9956-8354
University of Utah · USVellore Institute of Technology University · IN

Funding

UTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jared P Rutter · 1986 to 2026
$72.6M
X-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6M
Structure, function and regulation of the H2B ubiquitin-conjugating complexR01GM127783 · NIGMS · UNIVERSITY OF UTAH · PI CHANDRASEKHARAN, MAHESH B · 2018 to 2022
$1.7M
Q-ToF Mass Spectrometer for the University of Utah MS and Proteomics CoreS10OD018210 · OD · UNIVERSITY OF UTAH · PI COX, JAMES ERIC · 2015 to 2015
$530k
A versatile "pan-spike-in" internal reference genome methodology for quantitative ChIP-seq normalizationR21HG011520 · NHGRI · UNIVERSITY OF UTAH · PI CHANDRASEKHARAN, MAHESH B · 2021 to 2022
$419k
NCI NIH HHS P30 CA042014NHGRI NIH HHS R21 HG011520NIGMS NIH HHS P41 GM103393NIGMS NIH HHS R01 GM127783NIH HHS S10 OD018210
6 · The paper itself

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.

Indexed as

HistonesSaccharomyces cerevisiae ProteinsUbiquitin-Conjugating EnzymesChromatinHumansSaccharomyces cerevisiaeUbiquitinBre1 protein, S cerevisiaeChromatinHistonesRAD6 protein, S cerevisiaeSaccharomyces cerevisiae ProteinsUbiquitinUbiquitin-Conjugating Enzymes

Identifiers

PMID36715322
PMCPMC10018343
OpenAlexW4318478785

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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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.