Evidence map›Paper›PMID 35390161›Full record

ArticleNucleic acids research2022

Multivalent DNA and nucleosome acidic patch interactions specify VRK1 mitotic localization and activity.

Gabrielle R Budziszewski, Yani Zhao, Cathy J Spangler, Katarzyna M Kedziora, Michael R Williams, Dalal N Azzam, Aleksandra Skrajna, Yuka Koyama, Andrew P Cesmat, Holly C Simmons and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
4.2field-weighted citation impact, top 4% 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

17 citing papers in PubMed, 51 citations in OpenAlex.

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  5. Haspin kinase binds to a nucleosomal DNA supergroove.Nature structural & molecular biology · 2025
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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

14 authors at 1 institution in 1 country.

Gabrielle R BudziszewskiDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA.
Yani ZhaoDivision of Chemical Biology and Medicinal Chemistry, Center for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA.
Cathy J SpanglerDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA.
Katarzyna M KedzioraBioinformatics and Analytics Research Collaborative, University of North Carolina, Chapel Hill, NC, USA.
Michael R WilliamsDivision of Chemical Biology and Medicinal Chemistry, Center for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA.
Dalal N AzzamDivision of Chemical Biology and Medicinal Chemistry, Center for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA.
Aleksandra SkrajnaDivision of Chemical Biology and Medicinal Chemistry, Center for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA.
Yuka KoyamaDivision of Chemical Biology and Medicinal Chemistry, Center for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA.
Andrew P CesmatDivision of Chemical Biology and Medicinal Chemistry, Center for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA.
Holly C SimmonsDivision of Chemical Biology and Medicinal Chemistry, Center for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA.
Eyla C ArteagaDivision of Chemical Biology and Medicinal Chemistry, Center for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA.
Joshua D StraussDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA.
Dmitri KireevDivision of Chemical Biology and Medicinal Chemistry, Center for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA.
Robert K McGintyDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA.ORCID 0000-0001-9641-7350
University of North Carolina at Chapel Hill · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI David Darr · 1985 to 2026
$201.5M
Molecular Mechanisms of Chromatin RecognitionR35GM133498 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Robert McGinty · 2019 to 2026
$3.3M
Cancer Epigenetics Training GrantT32CA217824 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WEISSMAN, BERNARD E. · 2017 to 2021
$1.8M
Training in Mechanistic, Interdisciplinary Studies of Biological SystemsT32GM119999 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RAMSDEN, DALE A · 2017 to 2021
$1.2M
Computational and experimental insights into the structure and dynamics of heterochromatinR01GM132299 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HATHAWAY, NATHANIEL A., KIREEV, DMITRI · 2020 to 2023
$1.2M
Structure-Guided Mechanistic Studies of Dot1L in Mixed Lineage LeukemiaF99CA253730 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SPANGLER, CATHERINE JEANETTE · 2020 to 2021
$76k
NCI NIH HHS F99 CA253730NCI NIH HHS P30 CA016086NCI NIH HHS T32 CA217824NIGMS NIH HHS R01 GM132299NIGMS NIH HHS R35 GM133498NIGMS NIH HHS T32 GM119999
6 · The paper itself

Abstract

A key role of chromatin kinases is to phosphorylate histone tails during mitosis to spatiotemporally regulate cell division. Vaccinia-related kinase 1 (VRK1) is a serine-threonine kinase that phosphorylates histone H3 threonine 3 (H3T3) along with other chromatin-based targets. While structural studies have defined how several classes of histone-modifying enzymes bind to and function on nucleosomes, the mechanism of chromatin engagement by kinases is largely unclear. Here, we paired cryo-electron microscopy with biochemical and cellular assays to demonstrate that VRK1 interacts with both linker DNA and the nucleosome acidic patch to phosphorylate H3T3. Acidic patch binding by VRK1 is mediated by an arginine-rich flexible C-terminal tail. Homozygous missense and nonsense mutations of this acidic patch recognition motif in VRK1 are causative in rare adult-onset distal spinal muscular atrophy. We show that these VRK1 mutations interfere with nucleosome acidic patch binding, leading to mislocalization of VRK1 during mitosis, thus providing a potential new molecular mechanism for pathogenesis.

Indexed as

HistonesNucleosomesChromatinCryoelectron MicroscopyDNAIntracellular Signaling Peptides and ProteinsPhosphorylationProtein Serine-Threonine KinasesThreonineChromatinDNAHistonesIntracellular Signaling Peptides and ProteinsNucleosomesProtein Serine-Threonine KinasesThreonineVRK1 protein, human

Identifiers

PMID35390161
PMCPMC9071384
OpenAlexW4225919587

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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.