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Reto Gassmann¹, Ana Carvalho^1,4, Alexander J. Henzing¹, Sandrine Ruchaud¹, Damien F. Hudson¹, Reiko Honda³, Erich A. Nigg³, Dietlind L. Gerloff², and William C. Earnshaw¹

¹ Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JR, Scotland, UK
² Institute of Structural and Molecular Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JR, Scotland, UK
³ Max Planck Institute for Biochemistry, D-82152 Martinsried, Germany
⁴ Institute of Molecular Pathology and Immunology of the University of Porto, University of Porto, Porto, Portugal

Address correspondence to W.C. Earnshaw, Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Kings Buildings, Mayfield Rd., Edinburgh EH9 3JR, Scotland, UK. Tel.: 44-131-650-7101. Fax: 44-131-650-7100. email: bill.earnshaw{at}ed.ac.uk

The chromosomal passenger complex of Aurora B kinase, INCENP, and Survivin has essential regulatory roles at centromeres and the central spindle in mitosis. Here, we describe Borealin, a novel member of the complex. Approximately half of Aurora B in mitotic cells is complexed with INCENP, Borealin, and Survivin; and Borealin binds Survivin and INCENP in vitro. A second complex contains Aurora B and INCENP, but no Borealin or Survivin. Depletion of Borealin by RNA interference delays mitotic progression and results in kinetochore–spindle misattachments and an increase in bipolar spindles associated with ectopic asters. The extra poles, which apparently form after chromosomes achieve a bipolar orientation, severely disrupt the partitioning of chromosomes in anaphase. Borealin depletion has little effect on histone H3 serine¹⁰ phosphorylation. These results implicate the chromosomal passenger holocomplex in the maintenance of spindle integrity and suggest that histone H3 serine¹⁰ phosphorylation is performed by an Aurora B–INCENP subcomplex.

Key Words: mitosis; Aurora B kinase; Survivin; INCENP; TD-60

R. Honda's present address is Laboratory of Molecular Biophysics, University of Oxford, South Parks Rd., Oxford OX1 3QU, England, UK.

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