title: CENP-V is required for centromere organization, chromosome alignment and cytokinesis.
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.
authors.affiliation: Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Ana Mafalda Baptista
authors.initials: AM
authors.lastname: Tadeu
authors.forename: Susana
authors.initials: S
authors.lastname: Ribeiro
authors.forename: Josiah
authors.initials: J
authors.lastname: Johnston
authors.forename: Ilya
authors.initials: I
authors.lastname: Goldberg
authors.forename: Dietlind
authors.initials: D
authors.lastname: Gerloff
authors.forename: William C
authors.initials: WC
authors.lastname: Earnshaw
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002503:Centromere / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone; D002877:Chromosomes, Human / Q000378:metabolism* / Q000648:ultrastructure; D048749:Cytokinesis / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006570:Heterochromatin / Q000378:metabolism; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D034622:RNA Interference; D016415:Sequence Alignment
chemical_list: C532477:CENPV protein, human; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006570:Heterochromatin; C496644:SGO1 protein, human
references.citation: Cell. 2007 Jan 12;128(1):101-14
references.pmid: 17218258
references.citation: Trends Cell Biol. 2005 Nov;15(11):589-98
references.pmid: 16214339
references.citation: Cell Cycle. 2003 Nov-Dec;2(6):507-10
references.pmid: 14504461
references.citation: Nat Cell Biol. 2006 Oct;8(10):1133-42
references.pmid: 16998479
references.citation: Nature. 2001 Mar 1;410(6824):120-4
references.pmid: 11242054
references.citation: J Cell Sci. 1991 Apr;98 ( Pt 4):443-61
references.pmid: 1860899
references.citation: EMBO J. 2003 Apr 1;22(7):1599-607
references.pmid: 12660166
references.citation: Nature. 2002 Sep 26;419(6905):407-11
references.pmid: 12353038
references.citation: Curr Biol. 2007 May 1;17(9):741-8
references.pmid: 17412588
references.citation: Cell. 2007 Feb 23;128(4):693-705
references.pmid: 17320507
references.citation: J Cell Sci. 2004 Nov 1;117(Pt 23):5461-77
references.pmid: 15509863
references.citation: Curr Biol. 2006 Jul 25;16(14):1414-21
references.pmid: 16860740
references.citation: Mol Cell Biol. 2005 Dec;25(23):10315-28
references.pmid: 16287847
references.citation: Dev Cell. 2006 Nov;11(5):741-50
references.pmid: 17084365
references.citation: Chromosoma. 2005 Feb;113(7):385-97
references.pmid: 15609038
references.citation: EMBO J. 1991 May;10(5):1245-54
references.pmid: 2022189
references.citation: J Cell Biol. 2007 May 7;177(3):413-24
references.pmid: 17485487
references.citation: Annu Rev Cell Dev Biol. 1995;11:471-95
references.pmid: 8689566
references.citation: Cell. 2004 Dec 29;119(7):941-53
references.pmid: 15620353
references.citation: J Cell Biol. 2007 Mar 26;176(7):919-28
references.pmid: 17389228
references.citation: Dev Cell. 2003 Aug;5(2):323-36
references.pmid: 12919682
references.citation: Science. 2002 Nov 1;298(5595):1039-43
references.pmid: 12351676
references.citation: J Mol Biol. 2000 Sep 8;302(1):205-17
references.pmid: 10964570
references.citation: Trends Cell Biol. 2006 Feb;16(2):70-8
references.pmid: 16412639
references.citation: Proteins. 1997 Jul;28(3):405-20
references.pmid: 9223186
references.citation: Nature. 2001 May 24;411(6836):494-8
references.pmid: 11373684
references.citation: Nat Rev Mol Cell Biol. 2008 Jan;9(1):33-46
references.pmid: 18097444
references.citation: J Cell Biol. 2006 Jun 19;173(6):833-7
references.pmid: 16769825
references.citation: J Biol Chem. 2005 Jan 28;280(4):2826-30
references.pmid: 15548539
references.citation: Annu Rev Genomics Hum Genet. 2006;7:301-13
references.pmid: 16756479
references.citation: Trends Biochem Sci. 2005 Apr;30(4):172-5
references.pmid: 15817392
references.citation: Bioinformatics. 2004 Feb 12;20(3):426-7
references.pmid: 14960472
references.citation: Mol Cell. 2003 Dec;12(6):1591-8
references.pmid: 14690610
references.citation: Nat Rev Mol Cell Biol. 2007 Oct;8(10):798-812
references.pmid: 17848966
references.citation: J Cell Biol. 2001 Jun 11;153(6):1209-26
references.pmid: 11402065
references.citation: J Cell Biol. 2004 Jul 19;166(2):179-91
references.pmid: 15249581
references.citation: Nat Cell Biol. 2002 Jan;4(1):89-93
references.pmid: 11780129
references.citation: Mol Biol Cell. 2002 Jan;13(1):25-39
references.pmid: 11809820
references.citation: Dev Cell. 2004 Nov;7(5):637-51
references.pmid: 15525526
references.citation: Dev Cell. 2006 Jul;11(1):57-68
references.pmid: 16824953
references.citation: Science. 2001 Dec 21;294(5551):2539-42
references.pmid: 11598266
references.citation: Trends Cell Biol. 2001 Jun;11(6):266-73
references.pmid: 11356363
references.citation: Dev Cell. 2001 Dec;1(6):759-70
references.pmid: 11740938
references.citation: Nature. 2000 Jan 6;403(6765):41-5
references.pmid: 10638745
references.citation: Nat Struct Mol Biol. 2004 Nov;11(11):1076-83
references.pmid: 15475964
references.citation: Curr Biol. 2005 Feb 22;15(4):353-9
references.pmid: 15723797
references.citation: Genes Dev. 2007 Feb 15;21(4):420-35
references.pmid: 17322402
references.citation: Braz J Med Biol Res. 2002 May;35(5):499-507
references.pmid: 12011934
references.citation: Curr Opin Genet Dev. 2006 Apr;16(2):125-36
references.pmid: 16503131
references.citation: J Cell Sci. 2003 Jul 15;116(Pt 14):2987-98
references.pmid: 12783991
references.citation: J Mol Biol. 1990 Oct 5;215(3):403-10
references.pmid: 2231712
references.citation: J Cell Biol. 2002 Sep 2;158(5):915-27
references.pmid: 12196509
references.citation: Genes Dev. 2004 Jun 1;18(11):1251-62
references.pmid: 15145825
references.citation: Nat Rev Mol Cell Biol. 2007 May;8(5):379-93
references.pmid: 17426725
references.citation: Mol Cell. 2003 Dec;12(6):1577-89
references.pmid: 14690609
references.citation: Chromosoma. 2004 Nov;113(5):211-22
references.pmid: 15351889
references.citation: Chromosoma. 1985;91(3-4):313-21
references.pmid: 2579778