Dissecting the roles of Haspin and VRK1 in histone H3 phosphorylation during mitosis

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)....

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Published in:Scientific reports 2022-07, Vol.12 (1), p.11210-11210, Article 11210
Main Authors: Cartwright, Tyrell N., Harris, Rebecca J., Meyer, Stephanie K., Mon, Aye M., Watson, Nikolaus A., Tan, Cheryl, Marcelot, Agathe, Wang, Fangwei, Zinn-Justin, Sophie, Traktman, Paula, Higgins, Jonathan M. G.
Format: Article
Language:English
Subjects:
631/337/100/2285
631/45/607/275
631/80
631/80/103
631/80/458/1733
631/80/641/1655
Cell division
Cell proliferation
Chromosomes
CRISPR
Histone H3
Histones
Humanities and Social Sciences
Kinases
Meiosis
Mitosis
multidisciplinary
Nervous system
Neuromuscular diseases
Phosphorylation
Protein kinase
RNA-mediated interference
Science
Science (multidisciplinary)
Threonine
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-022-15339-8