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Cited by 4Genomics and Chromatin DynamicsMicrotubule and mitosis dynamicsNuclear Structure and Function

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Haspin kinase binds to a nucleosomal DNA supergroove

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Hicks, Chad W., Gliech, Colin R., Rahman, Sanim, Zhang, Xiangbin, Eneim, Andrew S., Vasquez, Stacy J., Holland, Andrew J., Wolberger, Cynthia·2025·Nature Structural & Molecular Biology
DOI 10.1038/s41594-025-01502-yPMC PMC12170164

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Abstract

Phosphorylation of histone H3 threonine 3 (H3T3) by Haspin recruits the chromosomal passenger complex to the inner centromere and ensures proper cell cycle progression through mitosis. The mechanism by which Haspin binds to nucleosomes to phosphorylate H3T3 is not known. Here we report cryogenic electron microscopy structures of the human Haspin kinase domain bound to a nucleosome. In contrast with previous structures of histone-modifying enzymes, Haspin solely contacts the nucleosomal DNA, inserting into a supergroove formed by apposing major grooves of two DNA gyres. This binding mode provides a plausible mechanism by which Haspin can bind to nucleosomes in a condensed chromatin environment to phosphorylate H3T3. We identify key basic residues in the Haspin kinase domain that are essential for phosphorylation of nucleosomal histone H3 and binding to mitotic chromatin. Our structural data provide notable insight into a histone-modifying enzyme that binds to nucleosomes solely through DNA contacts.

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Metadata

Authors
Hicks, C. W., Gliech, C. R., Rahman, S., Zhang, X., Eneim, A. S., Vasquez, S. J., Holland, A. J., & Wolberger, C.
Affiliations
Johns Hopkins University (US)
Corresponding author
Wolberger, Cynthia
ORCID
Venue
Nature Structural & Molecular Biology
Publisher
Springer Science and Business Media LLC
Published
2025-02-20
Volume
32
Issue
6
Pages
1030-1037
ISSN
  • 1545-9985 (ISSN-L)
  • 1545-9993
DOI
10.1038/s41594-025-01502-y
PMC
PMC12170164
OpenAlex
W4407789774
Cited by
4
References
2
Citations by year
2026: 3 · 2025: 1
FWCI
1.20
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Structural & Molecular Biology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
  • National Institutes of Health (2r35gm130393-06)
  • National Cancer Institute (F31CA261154, F31CA271743, R01CA266199)
  • National Institute of General Medical Sciences (R01GM095822, R35-GM130393, R01GM133897, R01GM114119)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
Haspin kinase, nucleosome, chromosomal passenger complex, inner centromere, mitosis, histone-modifying enzymes, cryo-EM structure, chromatin condensation

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