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Haspin: a newly discovered regulator of mitotic chromosome behavior

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Abstract

The haspins are divergent members of the eukaryotic protein kinase family that are conserved in many eukaryotic lineages including animals, fungi, and plants. Recently-solved crystal structures confirm that the kinase domain of human haspin has unusual structural features that stabilize a catalytically active conformation and create a distinctive substrate binding site. Haspin localizes predominantly to chromosomes and phosphorylates histone H3 at threonine-3 during mitosis, particularly at inner centromeres. This suggests that haspin directly regulates chromosome behavior by modifying histones, although it is likely that additional substrates will be identified in the future. Depletion of haspin by RNA interference in human cell lines causes premature loss of centromeric cohesin from chromosomes in mitosis and failure of metaphase chromosome alignment, leading to activation of the spindle assembly checkpoint and mitotic arrest. Haspin overexpression stabilizes chromosome arm cohesion. Haspin, therefore, appears to be required for protection of cohesion at mitotic centromeres. Saccharomyces cerevisiae homologues of haspin, Alk1 and Alk2, are also implicated in regulation of mitosis. In mammals, haspin is expressed at high levels in the testis, particularly in round spermatids, so it seems likely that haspin has an additional role in post-meiotic spermatogenesis. Haspin is currently the subject of a number of drug discovery efforts, and the future use of haspin inhibitors should provide new insight into the cellular functions of these kinases and help determine the utility of, for example, targeting haspin for cancer therapy.

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References

  • Adams RR, Maiato H, Earnshaw WC, Carmena M (2001) Essential roles of Drosophila inner centromere protein (INCENP) and aurora B in histone H3 phosphorylation, metaphase chromosome alignment, kinetochore disjunction, and chromosome segregation. J Cell Biol 153:865–880

    Article  CAS  PubMed  Google Scholar 

  • Bonenfant D, Towbin H, Coulot M, Schindler P, Mueller DR, van Oostrum J (2007) Analysis of dynamic changes in post-translational modifications of human histones during cell cycle by mass spectrometry. Mol Cell Proteomics 6:1917–1932

    Article  CAS  PubMed  Google Scholar 

  • Caperta AD, Rosa M, Delgado M, Karimi R, Demidov D, Viegas W, Houben A (2008) Distribution patterns of phosphorylated Thr 3 and Thr 32 of histone H3 in plant mitosis and meiosis. Cytogenet Genome Res 122:73–79

    Article  CAS  PubMed  Google Scholar 

  • Casas-Mollano JA, Jeong BR, Xu J, Moriyama H, Cerutti H (2008) The MUT9p kinase phosphorylates histone H3 threonine 3 and is necessary for heritable epigenetic silencing in Chlamydomonas. Proc Natl Acad Sci U S A 105:6486–6491

    Article  CAS  PubMed  Google Scholar 

  • Chignola F, Gaetani M, Rebane A, Org T, Mollica L, Zucchelli C, Spitaleri A, Mannella V, Peterson P, Musco G (2009) The solution structure of the first PHD finger of autoimmune regulator in complex with non-modified histone H3 tail reveals the antagonistic role of H3R2 methylation. Nucleic Acids Res 37:2951–2961

    Article  CAS  PubMed  Google Scholar 

  • Couture JF, Collazo E, Trievel RC (2006) Molecular recognition of histone H3 by the WD40 protein WDR5. Nat Struct Mol Biol 13:698–703

    Article  CAS  PubMed  Google Scholar 

  • Crosio C, Fimia GM, Loury R, Kimura M, Okano Y, Zhou H, Sen S, Allis CD, Sassone-Corsi P (2002) Mitotic phosphorylation of histone H3: spatio-temporal regulation by mammalian Aurora kinases. Mol Cell Biol 22:874–885

    Article  CAS  PubMed  Google Scholar 

  • Dai J, Higgins JMG (2005) Haspin: a mitotic histone kinase required for metaphase chromosome alignment. Cell Cycle 4:665–668

    CAS  PubMed  Google Scholar 

  • Dai J, Sultan S, Taylor SS, Higgins JMG (2005) The kinase haspin is required for mitotic histone H3 Thr 3 phosphorylation and normal metaphase chromosome alignment. Genes Dev 19:472–488

    Article  CAS  PubMed  Google Scholar 

  • Dai J, Sullivan BA, Higgins JMG (2006) Regulation of mitotic chromosome cohesion by haspin and Aurora B. Dev Cell 11:741–750

    Article  CAS  PubMed  Google Scholar 

  • Dai J, Kateneva AV, Higgins JMG (2009) Studies of haspin-depleted cells reveal that spindle-pole integrity in mitosis requires chromosome cohesion. J Cell Sci 122:4168–4176

    Article  CAS  PubMed  Google Scholar 

  • de Cárcer G, de Castro IP, Malumbres M (2007) Targeting cell cycle kinases for cancer therapy. Curr Med Chem 14:969–985

    Article  PubMed  Google Scholar 

  • de la Barre AE, Angelov D, Molla A, Dimitrov S (2001) The N-terminus of histone H2B, but not that of histone H3 or its phosphorylation, is essential for chromosome condensation. EMBO J 20:6383–6393

    Article  PubMed  Google Scholar 

  • Downes CS, Mullinger AM, Johnson RT (1991) Inhibitors of DNA topoisomerase II prevent chromatid separation in mammalian cells but do not prevent exit from mitosis. Proc Natl Acad Sci U S A 88:8895–8899

    Article  CAS  PubMed  Google Scholar 

  • Egli D, Birkhoff G, Eggan K (2008) Mediators of reprogramming: transcription factors and transitions through mitosis. Nat Rev Mol Cell Biol 9:505–516

    Article  CAS  PubMed  Google Scholar 

  • Eot-Houllier G, Fulcrand G, Watanabe Y, Magnaghi-Jaulin L, Jaulin C (2008) Histone deacetylase 3 is required for centromeric H3K4 deacetylation and sister chromatid cohesion. Genes Dev 22:2639–2644

    Article  CAS  PubMed  Google Scholar 

  • Eswaran J, Patnaik D, Filippakopoulos P, Wang F, Stein RL, Murray J, Higgins JMG, Knapp S (2009) Structure and functional characterization of the atypical human kinase haspin. Proc Natl Acad Sci USA 106:20198–20203

    Google Scholar 

  • Fischle W, Wang Y, Allis CD (2003) Binary switches and modification cassettes in histone biology and beyond. Nature 425:475–479

    Article  CAS  PubMed  Google Scholar 

  • Fischle W, Tseng BS, Dormann HL, Ueberheide BM, Garcia BA, Shabanowitz J, Hunt DF, Funabiki H, Allis CD (2005) Regulation of HP1-chromatin binding by histone H3 methylation and phosphorylation. Nature 438:1116–1122

    Article  CAS  PubMed  Google Scholar 

  • Flanagan JF, Mi LZ, Chruszcz M, Cymborowski M, Clines KL, Kim Y, Minor W, Rastinejad F, Khorasanizadeh S (2005) Double chromodomains cooperate to recognize the methylated histone H3 tail. Nature 438:1181–1185

    Article  CAS  PubMed  Google Scholar 

  • Garcia BA, Barber CM, Hake SB, Ptak C, Turner FB, Busby SA, Shabanowitz J, Moran RG, Allis CD, Hunt DF (2005) Modifications of human histone H3 variants during mitosis. Biochemistry 44:13202–13213

    Article  CAS  PubMed  Google Scholar 

  • Georgatos SD, Markaki Y, Christogianni A, Politou AS (2009) Chromatin remodeling during mitosis: a structure-based code? Front Biosci 14:2017–2027

    Article  CAS  PubMed  Google Scholar 

  • Giet R, Glover DM (2001) Drosophila aurora B kinase is required for histone H3 phosphorylation and condensin recruitment during chromosome condensation and to organize the central spindle during cytokinesis. J Cell Biol 152:669–682

    Article  CAS  PubMed  Google Scholar 

  • Gimenez-Abian JF, Sumara I, Hirota T, Hauf S, Gerlich D, de la Torre C, Ellenberg J, Peters JM (2004) Regulation of sister chromatid cohesion between chromosome arms. Curr Biol 14:1187–1193

    Article  CAS  PubMed  Google Scholar 

  • Hammoud SS, Nix DA, Zhang H, Purwar J, Carrell DT, Cairns BR (2009) Distinctive chromatin in human sperm packages genes for embryo development. Nature 460:473–478

    CAS  PubMed  Google Scholar 

  • Hans F, Dimitrov S (2001) Histone H3 phosphorylation and cell division. Oncogene 20:3021–3027

    Article  CAS  PubMed  Google Scholar 

  • Hauf S, Waizenegger IC, Peters JM (2001) Cohesin cleavage by separase required for anaphase and cytokinesis in human cells. Science 293:1320–1323

    Article  CAS  PubMed  Google Scholar 

  • Hauf S, Roitinger E, Koch B, Dittrich CM, Mechtler K, Peters JM (2005) Dissociation of cohesin from chromosome arms and loss of arm cohesion during early mitosis depends on phosphorylation of SA2. PLoS Biol 3:e69

    Article  PubMed  Google Scholar 

  • Hendzel MJ, Wei Y, Mancini MA, Van Hooser A, Ranalli T, Brinkley BR, Bazett-Jones DP, Allis CD (1997) Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation. Chromosoma 106:348–360

    Article  CAS  PubMed  Google Scholar 

  • Higgins JMG (2001a) Haspin-like proteins: A new family of evolutionarily conserved putative eukaryotic protein kinases. Prot Sci 10:1677–1684

    Article  CAS  Google Scholar 

  • Higgins JMG (2001b) The haspin gene: location in an intron of the Integrin αE gene, associated transcription of an Integrin αE-derived RNA and expression in diploid as well as haploid cells. Gene 267:55–69

    Article  CAS  PubMed  Google Scholar 

  • Higgins JMG (2003) Structure, function and evolution of haspin and haspin-related proteins, a distinctive group of eukaryotic protein kinases. Cell Mol Life Sci 60:446–462

    Article  CAS  PubMed  Google Scholar 

  • Hirota T, Lipp JJ, Toh BH, Peters JM (2005) Histone H3 serine 10 phosphorylation by Aurora B causes HP1 dissociation from heterochromatin. Nature 438:1176–1180

    Article  CAS  PubMed  Google Scholar 

  • Hou F, Chu CW, Kong X, Yokomori K, Zou H (2007) The acetyltransferase activity of San stabilizes the mitotic cohesin at the centromeres in a shugoshin-independent manner. J Cell Biol 177:587–597

    Article  CAS  PubMed  Google Scholar 

  • Houben A, Demidov D, Caperta AD, Karimi R, Agueci F, Vlasenko L (2007) Phosphorylation of histone H3 in plants—a dynamic affair. Biochim Biophys Acta 1769:308–315

    CAS  PubMed  Google Scholar 

  • Hsu JY, Sun ZW, Li X, Reuben M, Tatchell K, Bishop DK, Grushcow JM, Brame CJ, Caldwell JA, Hunt DF, Lin R, Smith MM, Allis CD (2000) Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes. Cell 102:279–291

    Article  CAS  PubMed  Google Scholar 

  • Kang TH, Park DY, Choi YH, Kim KJ, Yoon HS, Kim KT (2007) Mitotic histone H3 phosphorylation by vaccinia-related kinase 1 in mammalian cells. Mol Cell Biol 27:8533–8546

    Article  CAS  PubMed  Google Scholar 

  • Kannan N, Taylor SS, Zhai Y, Venter JC, Manning G (2007) Structural and functional diversity of the microbial kinome. PLoS Biol 5:e17

    Article  PubMed  Google Scholar 

  • Kitajima TS, Hauf S, Ohsugi M, Yamamoto T, Watanabe Y (2005) Human Bub1 defines the persistent cohesion site along the mitotic chromosome by affecting Shugoshin localization. Curr Biol 15:353–359

    Article  CAS  PubMed  Google Scholar 

  • Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima SA, Watanabe Y (2006) Shugoshin collaborates with protein phosphatase 2A to protect cohesin. Nature 441:46–52

    Article  CAS  PubMed  Google Scholar 

  • Koh AS, Kuo AJ, Park SY, Cheung P, Abramson J, Bua D, Carney D, Shoelson SE, Gozani O, Kingston RE, Benoist C, Mathis D (2008) Aire employs a histone-binding module to mediate immunological tolerance, linking chromatin regulation with organ-specific autoimmunity. Proc Natl Acad Sci U S A 105:15878–15883

    Article  CAS  PubMed  Google Scholar 

  • Kong X, Ball AR Jr, Sonoda E, Feng J, Takeda S, Fukagawa T, Yen TJ, Yokomori K (2009) Cohesin associates with spindle poles in a mitosis-specific manner and functions in spindle assembly in vertebrate cells. Mol Biol Cell 20:1289–1301

    Article  CAS  PubMed  Google Scholar 

  • Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705

    Article  CAS  PubMed  Google Scholar 

  • Lipp JJ, Hirota T, Poser I, Peters JM (2007) Aurora B controls the association of condensin I but not condensin II with mitotic chromosomes. J Cell Sci 120:1245–1255

    Article  CAS  PubMed  Google Scholar 

  • Loidl P (2004) A plant dialect of the histone language. Trends Plant Sci 9:84–90

    Article  CAS  PubMed  Google Scholar 

  • Losada A, Hirano M, Hirano T (1998) Identification of Xenopus SMC protein complexes required for sister chromatid cohesion. Genes Dev 12:1986–1997

    Article  CAS  PubMed  Google Scholar 

  • Losada A, Hirano M, Hirano T (2002) Cohesin release is required for sister chromatid resolution, but not for condensin-mediated compaction, at the onset of mitosis. Genes Dev 16:3004–3016

    Article  CAS  PubMed  Google Scholar 

  • MacCallum DE, Losada A, Kobayashi R, Hirano T (2002) ISWI remodeling complexes in Xenopus egg extracts: identification as major chromosomal components that are regulated by INCENP-aurora B. Mol Biol Cell 13:25–39

    Article  CAS  PubMed  Google Scholar 

  • Macdonald N, Welburn JP, Noble ME, Nguyen A, Yaffe MB, Clynes D, Moggs JG, Orphanides G, Thomson S, Edmunds JW, Clayton AL, Endicott JA, Mahadevan LC (2005) Molecular basis for the recognition of phosphorylated and phosphoacetylated histone H3 by 14–3–3. Mol Cell 20:199–211

    Article  CAS  PubMed  Google Scholar 

  • Markaki Y, Christogianni A, Politou AS, Georgatos SD (2009) Phosphorylation of histone H3 at Thr3 is part of a combinatorial pattern that marks and configures mitotic chromatin. J Cell Sci 122:2809–2819

    Article  CAS  PubMed  Google Scholar 

  • McGuinness BE, Hirota T, Kudo NR, Peters JM, Nasmyth K (2005) Shugoshin prevents dissociation of cohesin from centromeres during mitosis in vertebrate cells. PLoS Biol 3:e86

    Article  PubMed  Google Scholar 

  • Nasmyth K (2002) Segregating sister genomes: the molecular biology of chromosome separation. Science 297:559–565

    Article  CAS  PubMed  Google Scholar 

  • Nespoli A, Vercillo R, di Nola L, Diani L, Giannattasio M, Plevani P, Muzi-Falconi M (2006) Alk1 and Alk2 are two new cell cycle-regulated haspin-like proteins in budding yeast. Cell Cycle 5:1464–1471

    CAS  PubMed  Google Scholar 

  • Nigg EA (2001) Mitotic kinases as regulators of cell division and its checkpoints. Nat Rev Mol Cell Biol 2:21–32

    Article  CAS  PubMed  Google Scholar 

  • Nousiainen M, Sillje HH, Sauer G, Nigg EA, Korner R (2006) Phosphoproteome analysis of the human mitotic spindle. Proc Natl Acad Sci U S A 103:5391–5396

    Article  CAS  PubMed  Google Scholar 

  • Osman C, Merkwirth C, Langer T (2009) Prohibitins and the functional compartmentalization of mitochondrial membranes. J Cell Sci 122:3823–3830

    Article  CAS  PubMed  Google Scholar 

  • Patnaik D, Xian J, Glicksman MA, Cuny GD, Stein RL, Higgins JMG (2008) Identification of small molecule inhibitors of the mitotic kinase haspin by high throughput screening using a homogeneous time-resolved fluorescence resonance energy transfer assay. J Biomol Screen 13:1025–1034

    Article  CAS  PubMed  Google Scholar 

  • Peters JM, Tedeschi A, Schmitz J (2008) The cohesin complex and its roles in chromosome biology. Genes Dev 22:3089–3114

    Article  CAS  PubMed  Google Scholar 

  • Polioudaki H, Markaki Y, Kourmouli N, Dialynas G, Theodoropoulos PA, Singh PB, Georgatos SD (2004) Mitotic phosphorylation of histone H3 at threonine 3. FEBS Lett 560:39–44

    Article  CAS  PubMed  Google Scholar 

  • Riedel CG, Katis VL, Katou Y, Mori S, Itoh T, Helmhart W, Galova M, Petronczki M, Gregan J, Cetin B, Mudrak I, Ogris E, Mechtler K, Pelletier L, Buchholz F, Shirahige K, Nasmyth K (2006) Protein phosphatase 2A protects centromeric sister chromatid cohesion during meiosis I. Nature 441:53–61

    Article  CAS  PubMed  Google Scholar 

  • Rosasco-Nitcher SE, Lan W, Khorasanizadeh S, Stukenberg PT (2008) Centromeric Aurora-B activation requires TD-60, microtubules, and substrate priming phosphorylation. Science 319:469–472

    Article  CAS  PubMed  Google Scholar 

  • Ruchaud S, Carmena M, Earnshaw WC (2007) Chromosomal passengers: conducting cell division. Nat Rev Mol Cell Biol 8:798–812

    Article  CAS  PubMed  Google Scholar 

  • Salic A, Waters JC, Mitchison TJ (2004) Vertebrate shugoshin links sister centromere cohesion and kinetochore microtubule stability in mitosis. Cell 118:567–578

    Article  CAS  PubMed  Google Scholar 

  • Sauve DM, Anderson HJ, Ray JM, James WM, Roberge M (1999) Phosphorylation-induced rearrangement of the histone H3 NH2-terminal domain during mitotic chromosome condensation. J Cell Biol 145:225–235

    Article  CAS  PubMed  Google Scholar 

  • Schmidt M, Bastians H (2007) Mitotic drug targets and the development of novel anti-mitotic anticancer drugs. Drug Resist Updat 10:162–181

    Article  CAS  PubMed  Google Scholar 

  • Schneider R, Bannister AJ, Weise C, Kouzarides T (2004) Direct binding of INHAT to H3 tails disrupted by modifications. J Biol Chem 279:23859–23862

    Article  CAS  PubMed  Google Scholar 

  • Shamu CE, Murray AW (1992) Sister chromatid separation in frog egg extracts requires DNA topoisomerase II activity during anaphase. J Cell Biol 117:921–934

    Article  CAS  PubMed  Google Scholar 

  • Sims RJ 3rd, Reinberg D (2008) Is there a code embedded in proteins that is based on post-translational modifications? Nat Rev Mol Cell Biol 9:815–820

    Article  CAS  PubMed  Google Scholar 

  • Southall SM, Wong PS, Odho Z, Roe SM, Wilson JR (2009) Structural basis for the requirement of additional factors for MLL1 SET domain activity and recognition of epigenetic marks. Mol Cell 33:181–191

    Article  CAS  PubMed  Google Scholar 

  • Spellman PT, Sherlock G, Zhang MQ, Iyer VR, Anders K, Eisen MB, Brown PO, Botstein D, Futcher B (1998) Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol Biol Cell 9:3273–3297

    CAS  PubMed  Google Scholar 

  • Spence JM, Phua HH, Mills W, Carpenter AJ, Porter AC, Farr CJ (2007) Depletion of topoisomerase II alpha leads to shortening of the metaphase interkinetochore distance and abnormal persistence of PICH-coated anaphase threads. J Cell Sci 120:3952–3964

    Article  CAS  PubMed  Google Scholar 

  • Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403:41–45

    Article  CAS  PubMed  Google Scholar 

  • Sullivan BA, Karpen GH (2004) Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin. Nat Struct Mol Biol 11:1076–1083

    Article  CAS  PubMed  Google Scholar 

  • Sullivan M, Hornig NC, Porstmann T, Uhlmann F (2004) Studies on substrate recognition by the budding yeast separase. J Biol Chem 279:1191–1196

    Article  CAS  PubMed  Google Scholar 

  • Sumara I, Vorlaufer E, Stukenberg PT, Kelm O, Redemann N, Nigg EA, Peters JM (2002) The dissociation of cohesin from chromosomes in prophase is regulated by Polo-like kinase. Mol Cell 9:515–525

    Article  CAS  PubMed  Google Scholar 

  • Takata H, Matsunaga S, Morimoto A, Ma N, Kurihara D, Ono-Maniwa R, Nakagawa M, Azuma T, Uchiyama S, Fukui K (2007) PHB2 protects sister-chromatid cohesion in mitosis. Curr Biol 17:1356–1361

    Article  CAS  PubMed  Google Scholar 

  • Tanaka H, Yoshimura Y, Nishina Y, Nozaki M, Nojima H, Nishimune Y (1994) Isolation and characterization of cDNA clones specifically expressed in testicular germ cells. FEBS Letts 355:4–10

    Article  CAS  Google Scholar 

  • Tanaka H, Yoshimura Y, Nozaki M, Yomogida K, Tsuchida J, Tosaka Y, Habu T, Nakanishi T, Okada M, Nojima H, Nishimune Y (1999) Identification and characterization of a haploid germ cell-specific nuclear protein kinase (haspin) in spermatid nuclei and its effects on somatic cells. J Biol Chem 274:17049–17057

    Article  CAS  PubMed  Google Scholar 

  • Tanaka H, Iguchi N, Nakamura Y, Kohroki J, Egydio de Carvalho C, Nishimune Y (2001) Cloning and characterization of human haspin gene encoding haploid germ cell-specific nuclear protein kinase. Mol Hum Reprod 7:211–218

    Article  CAS  PubMed  Google Scholar 

  • Tang Z, Sun Y, Harley SE, Zou H, Yu H (2004) Human Bub1 protects centromeric sister-chromatid cohesion through Shugoshin during mitosis. Proc Natl Acad Sci U S A 101:18012–18017

    Article  CAS  PubMed  Google Scholar 

  • Tang Z, Shu H, Qi W, Mahmood NA, Mumby MC, Yu H (2006) PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation. Dev Cell 10:575–585

    Article  CAS  PubMed  Google Scholar 

  • Toyoda Y, Yanagida M (2006) Coordinated requirements of human topo II and cohesin for metaphase centromere alignment under Mad2-dependent spindle checkpoint surveillance. Mol Biol Cell 17:2287–2302

    Article  CAS  PubMed  Google Scholar 

  • Tsou MF, Stearns T (2006) Mechanism limiting centrosome duplication to once per cell cycle. Nature 442:947–951

    Article  CAS  PubMed  Google Scholar 

  • Turner BM (1993) Decoding the nucleosome. Cell 75:5–8

    CAS  PubMed  Google Scholar 

  • Vagnarelli P, Ribeiro SA, Earnshaw WC (2008) Centromeres: old tales and new tools. FEBS Lett 582:1950–1959

    Article  CAS  PubMed  Google Scholar 

  • Villa F, Capasso P, Tortorici M, Forneris F, de Marco A, Mattevi A, Musacchio A (2009) Crystal structure of the catalytic domain of haspin, an atypical kinase implicated in chromatin organization. Proc Natl Acad Sci USA 106:20204–20209

    Google Scholar 

  • Waizenegger IC, Hauf S, Meinke A, Peters JM (2000) Two distinct pathways remove mammalian cohesin from chromosome arms in prophase and from centromeres in anaphase. Cell 103:399–410

    Article  CAS  PubMed  Google Scholar 

  • Wang LH, Schwarzbraun T, Speicher MR, Nigg EA (2008a) Persistence of DNA threads in human anaphase cells suggests late completion of sister chromatid decatenation. Chromosoma 117:123–135

    Article  PubMed  Google Scholar 

  • Wang X, Yang Y, Duan Q, Jiang N, Huang Y, Darzynkiewicz Z, Dai W (2008b) sSgo1, a major splice variant of Sgo1, functions in centriole cohesion where it is regulated by Plk1. Dev Cell 14:331–341

    Article  CAS  PubMed  Google Scholar 

  • Wei Y, Yu L, Bowen J, Gorovsky MA, Allis CD (1999) Phosphorylation of histone H3 is required for proper chromosome condensation and segregation. Cell 97:99–109

    Article  CAS  PubMed  Google Scholar 

  • Williams BC, Garrett-Engele CM, Li Z, Williams EV, Rosenman ED, Goldberg ML (2003) Two putative acetyltransferases, san and deco, are required for establishing sister chromatid cohesion in Drosophila. Curr Biol 13:2025–2036

    Article  CAS  PubMed  Google Scholar 

  • Wykes SM, Krawetz SA (2003) The structural organization of sperm chromatin. J Biol Chem 278:29471–29477

    Article  CAS  PubMed  Google Scholar 

  • Xu Z, Cetin B, Anger M, Cho US, Helmhart W, Nasmyth K, Xu W (2009) Structure and function of the PP2A-shugoshin interaction. Molecular Cell 35:426–441

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

I would like to thank Andrea Musacchio for communicating unpublished results, Stefan Knapp and Jun Dai for providing pictures for Figs. 1 and 2, and Anna Kateneva and Fangwei Wang for their comments on the manuscript. Work in the Higgins laboratory is supported by the American Cancer Society (RSG-05-134-01-GMC) and the National Institutes of Health (GM074210 and CA122608).

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  1. Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Smith Building Room 538A, 1 Jimmy Fund Way, Boston, MA, 02115, USA

    Jonathan M. G. Higgins

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Correspondence to Jonathan M. G. Higgins.

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Communicated by E. Nigg

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Higgins, J.M.G. Haspin: a newly discovered regulator of mitotic chromosome behavior. Chromosoma 119, 137–147 (2010). https://doi.org/10.1007/s00412-009-0250-4

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