Evidence map›Paper›PMID 40089476›Full record

ArticleNature communications2025

APC/C-mediated ubiquitylation of extranucleosomal histone complexes lacking canonical degrons.

Aleksandra Skrajna, Tatyana Bodrug, Raquel C Martinez-Chacin, Caleb B Fisher, Kaeli A Welsh, Holly C Simmons, Eyla C Arteaga, Jake M Simmons, Mohamed A Nasr, Kyle M LaPak and 9 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. 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

19 authors.

Aleksandra Skrajna *Division of Chemical Biology and Medicinal Chemistry and Center for Integrated Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
Tatyana Bodrug *Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Raquel C Martinez-ChacinLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Caleb B FisherDepartment of Biochemistry and Biophysics, UNC School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
Kaeli A WelshDepartment of Pharmacology, UNC School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
Holly C SimmonsDivision of Chemical Biology and Medicinal Chemistry and Center for Integrated Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-2186-1494
Eyla C ArteagaDivision of Chemical Biology and Medicinal Chemistry and Center for Integrated Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
Jake M SimmonsDivision of Chemical Biology and Medicinal Chemistry and Center for Integrated Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.ORCID http://orcid.org/0009-0003-6281-0391
Mohamed A NasrCurriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-1020-1012
Kyle M LaPakDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA.
Anh NguyenDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA.
Mai T HuynhDivision of Chemical Biology and Medicinal Chemistry and Center for Integrated Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
Isabel FargoDivision of Chemical Biology and Medicinal Chemistry and Center for Integrated Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.ORCID http://orcid.org/0009-0009-1832-9895
Joshua G WelfareDivision of Chemical Biology and Medicinal Chemistry and Center for Integrated Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
Yani ZhaoDivision of Chemical Biology and Medicinal Chemistry and Center for Integrated Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.ORCID http://orcid.org/0009-0007-2779-7290
David S LawrenceDivision of Chemical Biology and Medicinal Chemistry and Center for Integrated Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-0901-1617
Dennis GoldfarbCurriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-1584-5423
Nicholas G BrownLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA. nbrown1@med.unc.edu.ORCID http://orcid.org/0000-0002-6141-0164
Robert K McGintyDivision of Chemical Biology and Medicinal Chemistry and Center for Integrated Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA. rmcginty@email.unc.edu.ORCID http://orcid.org/0000-0001-9641-7350

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Resource for Biocomputing Visualization and InformaticsP41GM103311 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2012 to 2017
$8.2M
Spindle Assembly Checkpoint SilencingR35GM128855 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Nicholas Gene Brown · 2018 to 2026
$4.1M
Molecular Mechanisms of Chromatin RecognitionR35GM133498 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Robert McGinty · 2019 to 2026
$3.3M
Molecular and Cellular Biophysics Training GrantT32GM148376 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Matthew R Redinbo, Qi Zhang · 2024 to 2026
$1.4M
American Cancer Society (American Cancer Society, Inc.) 132609-PF-18-153-01-DMCAmerican Heart Association (American Heart Association, Inc.) 23PRE1025746NCI NIH HHS P30 CA016086NIGMS NIH HHS P41 GM103311NIGMS NIH HHS R35 GM128855NIGMS NIH HHS R35 GM133498NIGMS NIH HHS T32 GM148376NSF | Directorate for Education & Human Resources | Division of Graduate Education (DGE) DGE-1650116U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM128855U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) T32GM148376-01A1
6 · The paper itself

Abstract

Non-degradative histone ubiquitylation plays a myriad of well-defined roles in the regulation of gene expression and choreographing DNA damage repair pathways. In contrast, the contributions of degradative histone ubiquitylation on genomic processes has remained elusive. Recently, the APC/C has been shown to ubiquitylate histones to regulate gene expression in pluripotent cells, but the molecular mechanism is unclear. Here we show that despite directly binding to the nucleosome through subunit APC3, the APC/C is unable to ubiquitylate nucleosomal histones. In contrast, extranucleosomal H2A/H2B and H3/H4 complexes are broadly ubiquitylated by the APC/C in an unexpected manner. Using a combination of cryo-electron microscopy (cryo-EM) and biophysical and enzymatic assays, we demonstrate that APC8 and histone tails direct APC/C-mediated polyubiquitylation of core histones in the absence of traditional APC/C substrate degron sequences. Taken together, our work implicates APC/C-nucleosome tethering in the degradation of diverse chromatin-associated proteins and extranucleosomal histones for the regulation of transcription and the cell cycle and for preventing toxicity due to excess histone levels.

Indexed as

Anaphase-Promoting Complex-CyclosomeHistonesNucleosomesUbiquitinationCryoelectron MicroscopyDegronsHumansProtein BindingAnaphase-Promoting Complex-CyclosomeHistonesNucleosomes

Identifiers

PMID40089476
PMCPMC11910654

What OpenQuestion holds

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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.