ArticleNucleic acids research2022
Multivalent DNA and nucleosome acidic patch interactions specify VRK1 mitotic localization and activity.
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.
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Who cites it
17 citing papers in PubMed, 51 citations in OpenAlex.
- Structure-based discovery of selective vaccinia-related kinase 1 inhibitors and fluorogenic active-site probes.The Journal of biological chemistry · 2026Article
- Mechanisms of DNA methyltransferase 3A1-mediated DNA methylation of nucleosomes.The Journal of biological chemistry · 2026Article
- DeSciDe: a tool for unbiased literature searching and gene list curation unveils a new role for the acidic patch mutation H2A E92K.Molecular omics · 2025Article
- Post-translational modification of H2B C-terminal helix regulates nucleosome interactions and chromatin signaling.Nucleic acids research · 2025Article
- Haspin kinase binds to a nucleosomal DNA supergroove.Nature structural & molecular biology · 2025Article
- Identifying key palmitoylation-associated genes in endometriosis through genomic data analysis.BMC women's health · 2025Article
- APC/C-mediated ubiquitylation of extranucleosomal histone complexes lacking canonical degrons.Nature communications · 2025Article
- Nuclear functions regulated by the VRK1 kinase.Nucleus (Austin, Tex.) · 2024Review
- Multifaceted regulation of sirtuin 2 (Sirt2) deacetylase activity.The Journal of biological chemistry · 2024Article
- The nucleosome reference frame and standard geometries for octasomes.Biophysical reviews · 2024Review
- Pathogenic effects of Leu200Pro and Arg387His VRK1 protein variants on phosphorylation targets and H4K16 acetylation in distal hereditary motor neuropathy.Journal of molecular medicine (Berlin, Germany) · 2024Article
- VRK1 Regulates Sensitivity to Oxidative Stress by Altering Histone Epigenetic Modifications and the Nuclear Phosphoproteome in Tumor Cells.International journal of molecular sciences · 2024Article
- Targeting the epigenome to reinvigorate T cells for cancer immunotherapy.Military Medical Research · 2023Review
- The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase.Epigenetics & chromatin · 2023Article
- VRK1 Kinase Activity Modulating Histone H4K16 Acetylation Inhibited by SIRT2 and VRK-IN-1.International journal of molecular sciences · 2023Article
- Targeting Histone Epigenetic Modifications and DNA Damage Responses in Synthetic Lethality Strategies in Cancer?Cancers · 2022Article
- Dissecting the roles of Haspin and VRK1 in histone H3 phosphorylation during mitosis.Scientific reports · 2022Article
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
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.
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