Article
- The EMBO Journal (2008) 27, 2510 - 2522
- doi:10.1038/emboj.2008.175
Published online: 4 September 2008
Subject Category:
CENP-V is required for centromere organization, chromosome alignment and cytokinesisEMBO Open
Ana Mafalda Baptista Tadeu1,2, Susana Ribeiro1, Josiah Johnston3, Ilya Goldberg3, Dietlind Gerloff4 and William C Earnshaw1
- Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK
- Department of Biochemistry, PDBEB, Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
- Image Informatics and Computational Biology Unit, NIH, National Institute on Aging, Baltimore, MD, USA
- Department of Cellular and Molecular Pharmacology, Baskin School of Engineering, University of California, Santa Cruz, CA, USA
Correspondence to:
William C Earnshaw,
Wellcome Trust Centre for Cell Biology, The University of Edinburgh, Mayfield Road, Edinburgh, EH9 3JR, UK. Tel.: +44 0131 650 7101; Fax: +44 0132 650 7100;
E-mail: bill.earnshaw@ed.ac.uk
Received 16 December 2007; Accepted 31 July 2008
Abstract
The mechanism of mitotic chromosome condensation is poorly understood, but even less is known about the mechanism of formation of the primary constriction, or centromere. A proteomic analysis of mitotic chromosome scaffolds led to the identification of CENP-V, a novel kinetochore protein related to a bacterial enzyme that detoxifies formaldehyde, a by-product of histone demethylation in eukaryotic cells. Overexpression of CENP-V leads to hypercondensation of pericentromeric heterochromatin, a phenotype that is abolished by mutations in the putative catalytic site. CENP-V depletion in HeLa cells leads to abnormal expansion of the primary constriction of mitotic chromosomes, mislocalization and destabilization of the chromosomal passenger complex (CPC) and alterations in the distribution of H3K9me3 in interphase nucleoplasm. CENP-V-depleted cells suffer defects in chromosome alignment in metaphase, lagging chromosomes in anaphase, failure of cytokinesis and rapid cell death. CENP-V provides a novel link between centromeric chromatin, the primary constriction and the CPC.
Keywords:
- chromosome passenger complex,
- kinetochore,
- mitosis,
- pericentromeric heterochromatin,
- primary constriction
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