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Lookup NU author(s): Dr Tyrell Cartwright, Rebecca Harris, Dr Stephanie Meyer, Nikolaus Watson, Cheryl Tan, Professor Jonathan HigginsORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Protein kinases that phosphorylate histones are ideally-placed to influence the behavior of chromosomes during cell division. Indeed, a number of conserved histone phosphorylation events occur prominently during mitosis and meiosis in most eukaryotes, including on histone H3 at threonine-3 (H3T3ph). At least two kinases, Haspin and VRK1 (NHK-1/ballchen in Drosophila), have been proposed to carry out this modification. Phosphorylation of H3 by Haspin has defined roles in mitosis, but the significance of VRK1 activity towards histones in dividing cells has been unclear. Here, using in vitro kinase assays, KiPIK screening, RNA interference, and CRISPR/Cas9 approaches, we were unable to substantiate a direct role for VRK1, or its paralogue VRK2, in the phosphorylation of threonine-3 or serine-10 of Histone H3 in mitosis, although loss of VRK1 did slow cell proliferation. We conclude that the role of VRKs, and their more recently identified association with neuromuscular disease and importance in cancers of the nervous system, are unlikely to involve mitotic histone kinase activity. In contrast, Haspin is required to generate H3T3ph during mitosis.
Author(s): Cartwright TN, Harris RJ, Meyer SK, Mon AM, Watson NA, Tan C, Marcelot A, Wang F, Zinn-Justin S, Traktman P, Higgins JMG
Publication type: Article
Publication status: Published
Journal: Scientific Reports
Year: 2022
Volume: 12
Print publication date: 01/07/2022
Online publication date: 01/07/2022
Acceptance date: 22/06/2022
Date deposited: 14/07/2022
ISSN (electronic): 2045-2322
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41598-022-15339-8
DOI: 10.1038/s41598-022-15339-8
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