O-GlcNAc transferase regulates mitotic chromatin dynamics

Kaoru Sakabe, Gerald Warren Hart

Research output: Contribution to journalArticle

Abstract

Mitosis must faithfully divide the genome such that each progeny inherits the same genetic material. DNA condensation is crucial in ensuring that chromosomes are correctly attached to the mitotic spindle for segregation, preventing DNA breaks or constrictions from the contractile ring. Histones form an octameric complex of basic proteins important in regulating DNA organization and accessibility. Histone post-translational modifications are altered during mitosis, although the roles of these post-translational modifications remain poorly characterized. Here, we report that N-acetylglucosamine (O-GlcNAc) transferase (OGT), the enzyme catalyzing the addition of O-GlcNAc moieties to nuclear and cytoplasmic proteins at serine and threonine residues, regulates some aspects of mitotic chromatin dynamics. OGT protein amounts decrease during M phase. Modest overexpression of OGT alters mitotic histone post-translational modifications at Lys-9, Ser-10, Arg-17, and Lys-27 of histone H3. Overexpression of OGT also prevents mitotic phosphorylation of coactivator-associated arginine methyltransferase 1 (CARM1) and prevents its correct cellular localization during mitosis. Moreover, OGT overexpression results in an increase in abnormal chromosomal bridge formation. Together, these results show that regulating the amount of OGT during mitosis is important in ensuring correct chromosomal segregation during mitosis.

Original languageEnglish (US)
Pages (from-to)34460-34468
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number45
DOIs
StatePublished - Nov 5 2010

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Chromatin
Mitosis
Histones
Post Translational Protein Processing
DNA
Phosphorylation
Spindle Apparatus
Proteins
DNA Breaks
Acetylglucosamine
Threonine
Chromosomes
Nuclear Proteins
Constriction
Cell Division
Serine
O-GlcNAc transferase
Condensation
Genes
Genome

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

O-GlcNAc transferase regulates mitotic chromatin dynamics. / Sakabe, Kaoru; Hart, Gerald Warren.

In: Journal of Biological Chemistry, Vol. 285, No. 45, 05.11.2010, p. 34460-34468.

Research output: Contribution to journalArticle

Sakabe, Kaoru ; Hart, Gerald Warren. / O-GlcNAc transferase regulates mitotic chromatin dynamics. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 45. pp. 34460-34468.
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