QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Research Data All Versions of this Article: gad.1267105v1 19/4/472    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dai, J. Articles by Higgins, J. M.G. Search for Related Content PubMed PubMed Citation Articles by Dai, J. Articles by Higgins, J. M.G. Social Bookmarking                   What's this?

RESEARCH PAPER

The kinase haspin is required for mitotic histone H3 Thr 3 phosphorylation and normal metaphase chromosome alignment

¹ Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA; ² Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom

Post-translational modifications of conserved N-terminal tail residues in histones regulate many aspects of chromosome activity. Thr 3 of histone H3 is highly conserved, but the significance of its phosphorylation is unclear, and the identity of the corresponding kinase unknown. Immunostaining with phospho-specific antibodies in mammalian cells reveals mitotic phosphorylation of H3 Thr 3 in prophase and its dephosphorylation during anaphase. Furthermore we find that haspin, a member of a distinctive group of protein kinases present in diverse eukaryotes, phosphorylates H3 at Thr 3 in vitro. Importantly, depletion of haspin by RNA interference reveals that this kinase is required for H3 Thr 3 phosphorylation in mitotic cells. In addition to its chromosomal association, haspin is found at the centrosomes and spindle during mitosis. Haspin RNA interference causes misalignment of metaphase chromosomes, and overexpression delays progression through early mitosis. This work reveals a new kinase involved in composing the histone code and adds haspin to the select group of kinases that integrate regulation of chromosome and spindle function during mitosis and meiosis.

[Keywords: Chromatin; centromere; mitosis; serine/threonine kinase; histone modification; chromosome congression]

Received September 29, 2004; revised version accepted December 17, 2004.

Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1267105.

³ Corresponding author.

E-MAIL jhiggins{at}rics.bwh.harvard.edu; FAX (617) 525-1010.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				T.-H. Kang, D.-Y. Park, Y. H. Choi, K.-J. Kim, H. S. Yoon, and K.-T. Kim Mitotic Histone H3 Phosphorylation by Vaccinia-Related Kinase 1 in Mammalian Cells Mol. Cell. Biol., December 15, 2007; 27(24): 8533 - 8546. [Abstract] [Full Text] [PDF]

				K. Tokuhiro, Y. Miyagawa, S. Yamada, M. Hirose, H. Ohta, Y. Nishimune, and H. Tanaka The 193-Base Pair Gsg2 (Haspin) Promoter Region Regulates Germ Cell-Specific Expression Bidirectionally and Synchronously Biol Reprod, March 1, 2007; 76(3): 407 - 414. [Abstract] [Full Text] [PDF]