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The functional role for condensin in the regulation of chromosomal organization during the cell cycle

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Abstract

In all organisms, the control of cell cycle progression is a fundamental process that is essential for cell growth, development, and survival. Through each cell cycle phase, the regulation of chromatin organization is essential for natural cell proliferation and maintaining cellular homeostasis. During mitosis, the chromatin morphology is dramatically changed to have a “thread-like” shape and the condensed chromosomes are segregated equally into two daughter cells. Disruption of the mitotic chromosome architecture physically impedes chromosomal behaviors, such as chromosome alignment and chromosome segregation; therefore, the proper mitotic chromosome structure is required to maintain chromosomal stability. Accumulating evidence has demonstrated that mitotic chromosome condensation is induced by condensin complexes. Moreover, recent studies have shown that condensin also modulates interphase chromatin and regulates gene expression. This review mainly focuses on the molecular mechanisms that condensin uses to exert its functions during the cell cycle progression. Moreover, we discuss the condensin-mediated chromosomal organization in cancer cells.

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References

  1. Hirano T (2016) Condensin-based chromosome organization from bacteria to vertebrates. Cell 164:847–857

    Article  CAS  PubMed  Google Scholar 

  2. Lau AC, Csankovszki G (2015) Condensin-mediated chromosome organization and gene regulation. Front Genet 5:473

    Article  PubMed  PubMed Central  Google Scholar 

  3. Li W, Hu Y, Oh S, Ma Q, Merkurjev D, Song X, Zhou X, Liu Z, Tanasa B, He X, Chen AY, Ohgi K, Zhang J, Liu W, Rosenfeld MG (2015) Condensin I and II complexes license full estrogen receptor alpha-dependent enhancer activation. Mol Cell 59:188–202

    Article  CAS  PubMed  Google Scholar 

  4. Nagasaka K, Hossain MJ, Roberti MJ, Ellenberg J, Hirota T (2016) Sister chromatid resolution is an intrinsic part of chromosome organization in prophase. Nat Cell Biol 18:692–699

    Article  CAS  PubMed  Google Scholar 

  5. Houlard M, Godwin J, Metson J, Lee J, Hirano T, Nasmyth K (2015) Condensin confers the longitudinal rigidity of chromosomes. Nat Cell Biol 17:771–781

    Article  CAS  PubMed  Google Scholar 

  6. Hirota T, Gerlich D, Koch B, Ellenberg J, Peters JM (2004) Distinct functions of condensin I and II in mitotic chromosome assembly. J Cell Sci 117:6435–6445

    Article  CAS  PubMed  Google Scholar 

  7. Ono T, Fang Y, Spector DL, Hirano T (2004) Spatial and temporal regulation of Condensins I and II in mitotic chromosome assembly in human cells. Mol Biol Cell 15:3296–3308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Takemoto A, Kimura K, Yokoyama S, Hanaoka F (2004) Cell cycle-dependent phosphorylation, nuclear localization, and activation of human condensin. J Biol Chem 279:4551–4559

    Article  CAS  PubMed  Google Scholar 

  9. Abe S, Nagasaka K, Hirayama Y, Kozuka-Hata H, Oyama M, Aoyagi Y, Obuse C, Hirota T (2011) The initial phase of chromosome condensation requires Cdk1-mediated phosphorylation of the CAP-D3 subunit of condensin II. Genes Dev 25:863–874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Piazza I, Haering CH, Rutkowska A (2013) Condensin: crafting the chromosome landscape. Chromosoma 122:175–190

    Article  CAS  PubMed  Google Scholar 

  11. Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villen J, Li J, Cohn MA, Cantley LC, Gygi SP (2004) Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci USA 101:12130–12135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ (2007) ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316:1160–1166

    Article  CAS  PubMed  Google Scholar 

  14. Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, Nardone J, Lee K, Reeves C, Li Y, Hu Y, Tan Z, Stokes M, Sullivan L, Mitchell J, Wetzel R, Macneill J, Ren JM, Yuan J, Bakalarski CE, Villen J, Kornhauser JM, Smith B, Li D, Zhou X, Gygi SP, Gu TL, Polakiewicz RD, Rush J, Comb MJ (2007) Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131:1190–1203

    Article  CAS  PubMed  Google Scholar 

  15. Stokes MP, Rush J, Macneill J, Ren JM, Sprott K, Nardone J, Yang V, Beausoleil SA, Gygi SP, Livingstone M, Zhang H, Polakiewicz RD, Comb MJ (2007) Profiling of UV-induced ATM/ATR signaling pathways. Proc Natl Acad Sci USA 104:19855–19860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP (2008) A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci USA 105:10762–10767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Li J, Rix U, Fang B, Bai Y, Edwards A, Colinge J, Bennett KL, Gao J, Song L, Eschrich S, Superti-Furga G, Koomen J, Haura EB (2010) A chemical and phosphoproteomic characterization of dasatinib action in lung cancer. Nat Chem Biol 6:291–299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal 3:ra3

    Article  PubMed  Google Scholar 

  19. Hegemann B, Hutchins JR, Hudecz O, Novatchkova M, Rameseder J, Sykora MM, Liu S, Mazanek M, Lenart P, Heriche JK, Poser I, Kraut N, Hyman AA, Yaffe MB, Mechtler K, Peters JM (2011) Systematic phosphorylation analysis of human mitotic protein complexes. Sci Signal 4:rs12

    Article  PubMed  PubMed Central  Google Scholar 

  20. Hsu PP, Kang SA, Rameseder J, Zhang Y, Ottina KA, Lim D, Peterson TR, Choi Y, Gray NS, Yaffe MB, Marto JA, Sabatini DM (2011) The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332:1317–1322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kettenbach AN, Schweppe DK, Faherty BK, Pechenick D, Pletnev AA, Gerber SA (2011) Quantitative phosphoproteomics identifies substrates and functional modules of Aurora and Polo-like kinase activities in mitotic cells. Sci Signal 4:rs5

    Article  CAS  PubMed  Google Scholar 

  22. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B (2011) System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal 4:rs3

    Article  PubMed  Google Scholar 

  23. Santamaria A, Wang B, Elowe S, Malik R, Zhang F, Bauer M, Schmidt A, Sillje HH, Korner R, Nigg EA (2011) The Plk1-dependent phosphoproteome of the early mitotic spindle. Mol Cell Proteom 10(M110):004457

    Google Scholar 

  24. Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA (2013) Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat Methods 10:634–637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sharma K, D’Souza RC, Tyanova S, Schaab C, Wisniewski JR, Cox J, Mann M (2014) Ultradeep human phosphoproteome reveals a distinct regulatory nature of Tyr and Ser/Thr-based signaling. Cell Rep 8:1583–1594

    Article  CAS  PubMed  Google Scholar 

  26. Yi T, Zhai B, Yu Y, Kiyotsugu Y, Raschle T, Etzkorn M, Seo HC, Nagiec M, Luna RE, Reinherz EL, Blenis J, Gygi SP, Wagner G (2014) Quantitative phosphoproteomic analysis reveals system-wide signaling pathways downstream of SDF-1/CXCR4 in breast cancer stem cells. Proc Natl Acad Sci USA 111:E2182–E2190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tada K, Susumu H, Sakuno T, Watanabe Y (2011) Condensin association with histone H2A shapes mitotic chromosomes. Nature 474:477–483

    Article  CAS  PubMed  Google Scholar 

  28. Kagami Y, Nihira K, Wada S, Ono M, Honda M, Yoshida K (2014) Mps1 phosphorylation of condensin II controls chromosome condensation at the onset of mitosis. J Cell Biol 205:781–790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Shintomi K, Takahashi TS, Hirano T (2015) Reconstitution of mitotic chromatids with a minimum set of purified factors. Nat Cell Biol 17:1014–1023

    Article  CAS  PubMed  Google Scholar 

  30. Liu W, Tanasa B, Tyurina OV, Zhou TY, Gassmann R, Liu WT, Ohgi KA, Benner C, Garcia-Bassets I, Aggarwal AK, Desai A, Dorrestein PC, Glass CK, Rosenfeld MG (2010) PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression. Nature 466:508–512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Piazza I, Rutkowska A, Ori A, Walczak M, Metz J, Pelechano V, Beck M, Haering CH (2014) Association of condensin with chromosomes depends on DNA binding by its HEAT-repeat subunits. Nat Struct Mol Biol 21:560–568

    Article  CAS  PubMed  Google Scholar 

  32. Takemoto A, Maeshima K, Ikehara T, Yamaguchi K, Murayama A, Imamura S, Imamoto N, Yokoyama S, Hirano T, Watanabe Y, Hanaoka F, Yanagisawa J, Kimura K (2009) The chromosomal association of condensin II is regulated by a noncatalytic function of PP2A. Nat Struct Mol Biol 16:1302–1308

    Article  CAS  PubMed  Google Scholar 

  33. Sullivan NL, Marquis KA, Rudner DZ (2009) Recruitment of SMC by ParB-parS organizes the origin region and promotes efficient chromosome segregation. Cell 137:697–707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kimura K, Hirano T (1997) ATP-dependent positive supercoiling of DNA by 13S condensin: a biochemical implication for chromosome condensation. Cell 90:625–634

    Article  CAS  PubMed  Google Scholar 

  35. Wilhelm L, Burmann F, Minnen A, Shin HC, Toseland CP, Oh BH, Gruber S (2015) SMC condensin entraps chromosomal DNA by an ATP hydrolysis dependent loading mechanism in Bacillus subtilis. Elife 4:06659

    Article  Google Scholar 

  36. Hudson DF, Ohta S, Freisinger T, Macisaac F, Sennels L, Alves F, Lai F, Kerr A, Rappsilber J, Earnshaw WC (2008) Molecular and genetic analysis of condensin function in vertebrate cells. Mol Biol Cell 19:3070–3079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kimura K, Hirano M, Kobayashi R, Hirano T (1998) Phosphorylation and activation of 13S condensin by Cdc2 in vitro. Science 282:487–490

    Article  CAS  PubMed  Google Scholar 

  38. Robellet X, Thattikota Y, Wang F, Wee TL, Pascariu M, Shankar S, Bonneil E, Brown CM, D’Amours D (2015) A high-sensitivity phospho-switch triggered by Cdk1 governs chromosome morphogenesis during cell division. Genes Dev 29:426–439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. St-Pierre J, Douziech M, Bazile F, Pascariu M, Bonneil E, Sauve V, Ratsima H, D’Amours D (2009) Polo kinase regulates mitotic chromosome condensation by hyperactivation of condensin DNA supercoiling activity. Mol Cell 34:416–426

    Article  CAS  PubMed  Google Scholar 

  40. Kinoshita K, Kobayashi TJ, Hirano T (2015) Balancing acts of two HEAT subunits of condensin I support dynamic assembly of chromosome axes. Dev Cell 33:94–106

    Article  CAS  PubMed  Google Scholar 

  41. George CM, Bozler J, Nguyen HQ, Bosco G (2014) Condensins are required for maintenance of nuclear architecture. Cells 3:865–882

    Article  PubMed  PubMed Central  Google Scholar 

  42. Buster DW, Daniel SG, Nguyen HQ, Windler SL, Skwarek LC, Peterson M, Roberts M, Meserve JH, Hartl T, Klebba JE, Bilder D, Bosco G, Rogers GC (2013) SCFSlimb ubiquitin ligase suppresses condensin II-mediated nuclear reorganization by degrading Cap-H2. J Cell Biol 201:49–63

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Nguyen HQ, Nye J, Buster DW, Klebba JE, Rogers GC, Bosco G (2015) Drosophila casein kinase I alpha regulates homolog pairing and genome organization by modulating condensin II subunit Cap-H2 levels. PLoS Genet 11:e1005014

    Article  PubMed  PubMed Central  Google Scholar 

  44. Yamashita D, Shintomi K, Ono T, Gavvovidis I, Schindler D, Neitzel H, Trimborn M, Hirano T (2011) MCPH1 regulates chromosome condensation and shaping as a composite modulator of condensin II. J Cell Biol 194:841–854

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Pferdehirt RR, Kruesi WS, Meyer BJ (2011) An MLL/COMPASS subunit functions in the C. elegans dosage compensation complex to target X chromosomes for transcriptional regulation of gene expression. Genes Dev 25:499–515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kim JH, Zhang T, Wong NC, Davidson N, Maksimovic J, Oshlack A, Earnshaw WC, Kalitsis P, Hudson DF (2013) Condensin I associates with structural and gene regulatory regions in vertebrate chromosomes. Nat Commun 4:2537

    PubMed  PubMed Central  Google Scholar 

  47. Dowen JM, Bilodeau S, Orlando DA, Hubner MR, Abraham BJ, Spector DL, Young RA (2013) Multiple structural maintenance of chromosome complexes at transcriptional regulatory elements. Stem Cell Rep 1:371–378

    Article  CAS  Google Scholar 

  48. Passerini V, Ozeri-Galai E, de Pagter MS, Donnelly N, Schmalbrock S, Kloosterman WP, Kerem B, Storchova Z (2016) The presence of extra chromosomes leads to genomic instability. Nat Commun 7:10754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ono T, Yamashita D, Hirano T (2013) Condensin II initiates sister chromatid resolution during S phase. J Cell Biol 200:429–441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Murakami-Tonami Y, Kishida S, Takeuchi I, Katou Y, Maris JM, Ichikawa H, Kondo Y, Sekido Y, Shirahige K, Murakami H, Kadomatsu K (2014) Inactivation of SMC2 shows a synergistic lethal response in MYCN-amplified neuroblastoma cells. Cell Cycle 13:1115–1131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Davalos V, Suarez-Lopez L, Castano J, Messent A, Abasolo I, Fernandez Y, Guerra-Moreno A, Espin E, Armengol M, Musulen E, Ariza A, Sayos J, Arango D, Schwartz S Jr (2012) Human SMC2 protein, a core subunit of human condensin complex, is a novel transcriptional target of the WNT signaling pathway and a new therapeutic target. J Biol Chem 287:43472–43481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Shiheido H, Naito Y, Kimura H, Genma H, Takashima H, Tokunaga M, Ono T, Hirano T, Du W, Yamada T (2012) Doi N, Iijima S, Hattori Y, Yanagawa H An anilinoquinazoline derivative inhibits tumor growth through interaction with hCAP-G2, a subunit of condensin II. PLoS One 7:e44889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Aleem E, Arceci RJ (2015) Targeting cell cycle regulators in hematologic malignancies. Front Cell Dev Biol 3:16

    Article  PubMed  PubMed Central  Google Scholar 

  54. Bavetsias V, Linardopoulos S (2015) Aurora kinase inhibitors: current status and outlook. Front Oncol 5:278

    Article  PubMed  PubMed Central  Google Scholar 

  55. Cholewa BD, Liu X, Ahmad N (2013) The role of polo-like kinase 1 in carcinogenesis: cause or consequence? Cancer Res 73:6848–6855

    Article  CAS  PubMed  Google Scholar 

  56. Dominguez-Brauer C, Thu KL, Mason JM, Blaser H, Bray MR, Mak TW (2015) Targeting mitosis in cancer: emerging strategies. Mol Cell 60:524–536

    Article  CAS  PubMed  Google Scholar 

  57. Marbouty M, Le Gall A, Cattoni DI, Cournac A, Koh A, Fiche JB, Mozziconacci J, Murray H, Koszul R, Nollmann M (2015) Condensin- and replication-mediated bacterial chromosome folding and origin condensation revealed by Hi-C and super-resolution imaging. Mol Cell 59:588–602

    Article  CAS  PubMed  Google Scholar 

  58. Webster M, Witkin KL, Cohen-Fix O (2009) Sizing up the nucleus: nuclear shape, size and nuclear-envelope assembly. J Cell Sci 122:1477–1486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by grants from the Jikei University Research Fund, the Jikei University Graduate Research Fund, the Japan Society for the Promotion of Science (KAKENHI Grant Number 26290041), Takeda Science Foundation, and the Vehicle Racing Commemorative Foundation.

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  1. Department of Biochemistry, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan

    Yuya Kagami & Kiyotsugu Yoshida

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  1. Yuya Kagami
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  2. Kiyotsugu Yoshida
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Correspondence to Kiyotsugu Yoshida.

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Kagami, Y., Yoshida, K. The functional role for condensin in the regulation of chromosomal organization during the cell cycle. Cell. Mol. Life Sci. 73, 4591–4598 (2016). https://doi.org/10.1007/s00018-016-2305-z

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