Histochemistry and Cell Biology

, Volume 125, Issue 1–2, pp 103–117

The microarchitecture of DNA replication domains

  • Anatoly A. Philimonenko
  • Zdeněk Hodný
  • Dean A. Jackson
  • Pavel Hozák
Original paper

Abstract

Most DNA synthesis in HeLa cell nucleus is concentrated in discrete foci. These synthetic sites can be identified by electron microscopy after allowing permeabilized cells to elongate nascent DNA in the presence of biotin-dUTP. Biotin incorporated into nascent DNA can be then immunolabeled with gold particles. Two types of DNA synthetic sites/replication factories can be distinguished at ultrastructural level: (1) electron-dense structures—replication bodies (RB), and (2) focal replication sites with no distinct underlying structure—replication foci (RF). The protein composition of these synthetic sites was studied using double immunogold labeling. We have found that both structures contain (a) proteins involved in DNA replication (DNA polymerase α, PCNA), (b) regulators of the cell cycle (cyclin A, cdk2), and (c) RNA processing components like Sm and SS-B/La auto antigens, p80-coilin, hnRNPs A1 and C1/C2. However, at least four regulatory and structural proteins (Cdk1, cyclin B1, PML and lamin B1) differ in their presence in RB and RF. Moreover, in contrast to RF, RB have structural organization. For example, while DNA polymerase α, PCNA and hnRNP A1 were diffusely spread throughout RB, hnRNP C1/C2 was found only at the very outside. Surprisingly, RB contained only small amounts of DNA. In conclusion, synthetic sites of both types contain similar but not the same sets of proteins. RB, however, have more developed microarchitecture, apparently with specific functional zones. This data suggest possible differences in genome regions replicated by these two types of replication factories.

Keywords

DNA replication Cell nucleus Ultrastructure Nuclear bodies Replication factory Replication foci Nuclear proteins 

Abbreviations

PCNA

Proliferating cell nuclear antigen

GFP

Green fluorescent protein

RB

Replication bodies

RF

Replication foci

References

  1. Adachi Y, Laemmli UK (1992) Identification of nuclear pre-replication centers poised for DNA synthesis in Xenopus egg extracts: immunolocalization study of replication protein A. J Cell Biol 119:1–15PubMedGoogle Scholar
  2. Alt JR, Cleveland JL, Hannink M, Diehl JA (2000) Phosphorylation-dependent regulation of cyclin D1 nuclear export and cyclin D1-dependent cellular transformation. Genes Dev 14:3102–3114PubMedGoogle Scholar
  3. Andrade LE, Chan EK, Raska I, Peebles CL, Roos G, Tan EM (1991) Human autoantibody to a novel protein of the nuclear coiled body: immunological characterization and cDNA cloning of p80-coilin. J Exp Med 173:1407–1419PubMedGoogle Scholar
  4. Andrade LE, Tan EM, Chan EK (1993) Immunocytochemical analysis of the coiled body in the cell cycle and during cell proliferation. Proc Natl Acad Sci U S A 90:1947–1951PubMedGoogle Scholar
  5. Bailly E, Pines J, Hunter T, Bornens M (1992) Cytoplasmic accumulation of cyclin B1 in human cells: association with a detergent-resistant compartment and with the centrosome. J Cell Sci 101(Pt 3):529–545PubMedGoogle Scholar
  6. Baldin V, Lukas J, Marcote MJ, Pagano M, Draetta G (1993) Cyclin D1 is a nuclear protein required for cell cycle progression in G1. Genes Dev 7:812–821PubMedGoogle Scholar
  7. Baudy P, Bram S (1978) Chromatin fiber dimensions and nucleosome orientation: a neutron scattering investigation. Nucleic Acids Res 5:3697–3714PubMedGoogle Scholar
  8. Bauer DW, Gall JG (1997) Coiled bodies without coilin. Mol Biol Cell 8:73–82PubMedGoogle Scholar
  9. Bellini M, Gall JG (1998) Coilin can form a complex with the U7 small nuclear ribonucleoprotein. Mol Biol Cell 9:2987–3001PubMedGoogle Scholar
  10. Bensch KG, Tanaka S, Hu SZ, Wang TS, Korn D (1982) Intracellular localization of human DNA polymerase alpha with monoclonal antibodies. J Biol Chem 257:8391–8396PubMedGoogle Scholar
  11. Blanchette M, Chabot B (1999) Modulation of exon skipping by high-affinity hnRNP A1-binding sites and by intron elements that repress splice site utilization. Embo J 18:1939–1952PubMedGoogle Scholar
  12. Blow JJ, Laskey RA (1986) Initiation of DNA replication in nuclei and purified DNA by a cell-free extract of Xenopus eggs. Cell 47:577–587PubMedGoogle Scholar
  13. Blow JJ, Laskey RA (1988) A role for the nuclear envelope in controlling DNA replication within the cell cycle. Nature 332:546–548PubMedGoogle Scholar
  14. Bouteille M, Kalifat SR, Delarue J (1967) Ultrastructural variations of nuclear bodies in human diseases. J Ultrastruct Res 19:474–486PubMedGoogle Scholar
  15. Brasch K, Ochs RL (1992) Nuclear bodies (NBs): a newly “rediscovered” organelle. Exp Cell Res 202:211–223PubMedGoogle Scholar
  16. Bravo R, Macdonald-Bravo H (1987) Existence of two populations of cyclin/proliferating cell nuclear antigen during the cell cycle: association with DNA replication sites. J Cell Biol 105:1549–1554PubMedGoogle Scholar
  17. Butz N, Ruetz S, Natt F, Hall J, Weiler J, Mestan J, Ducarre M, Grossenbacher R, Hauser P, Kempf D, Hofmann F (2005) The human ubiquitin-conjugating enzyme Cdc34 controls cellular proliferation through regulation of p27Kip1 protein levels. Exp Cell Res 303:482–493PubMedGoogle Scholar
  18. Cam H, Dynlacht BD (2003) Emerging roles for E2F: beyond the G1/S transition and DNA replication. Cancer Cell 3:311–316PubMedGoogle Scholar
  19. Cardoso MC, Leonhardt H, Nadal-Ginard B (1993) Reversal of terminal differentiation and control of DNA replication: cyclin A and Cdk2 specifically localize at subnuclear sites of DNA replication. Cell 74:979–992PubMedGoogle Scholar
  20. Cardoso MC, Joseph C, Rahn HP, Reusch R, Nadal-Ginard B, Leonhardt H (1997) Mapping and use of a sequence that targets DNA ligase I to sites of DNA replication in vivo. J Cell Biol 139:579–587PubMedGoogle Scholar
  21. Cayrol C, Knibiehler M, Ducommun B (1998) p21 binding to PCNA causes G1 and G2 cell cycle arrest in p53-deficient cells. Oncogene 16:311–320PubMedGoogle Scholar
  22. Chen J, Jackson PK, Kirschner MW, Dutta A (1995) Separate domains of p21 involved in the inhibition of Cdk kinase and PCNA. Nature 374:386–388PubMedGoogle Scholar
  23. Ching RW, Dellaire G, Eskiw CH, Bazett-Jones DP (2005) PML bodies: a meeting place for genomic loci? J Cell Sci 118:847–854PubMedGoogle Scholar
  24. Choi YD, Dreyfuss G (1984) Monoclonal antibody characterization of the C proteins of heterogeneous nuclear ribonucleoprotein complexes in vertebrate cells. J Cell Biol 99:1997–1204PubMedGoogle Scholar
  25. Cook PR (1991) The nucleoskeleton and the topology of replication. Cell 66:627–635PubMedGoogle Scholar
  26. Coverley D, Marr J, Ainscough J (2005) Ciz1 promotes mammalian DNA replication. J Cell Sci 118:101–112PubMedGoogle Scholar
  27. Dallaire F, Dupuis S, Fiset S, Chabot B (2000) Heterogeneous nuclear ribonucleoprotein A1 and UP1 protect mammalian telomeric repeats and modulate telomere replication in vitro. J Biol Chem 275:14509–14516PubMedGoogle Scholar
  28. DePamphilis ML (2003) The ‘ORC cycle’: a novel pathway for regulating eukaryotic DNA replication. Gene 310:1–15PubMedGoogle Scholar
  29. Derenzini M, Viron A, Puvion-Dutilleul F (1982) The Feulgen-like osmium-ammine reaction as a tool to investigate chromatin structure in thin sections. J Ultrastruct Res 80:133–147PubMedGoogle Scholar
  30. Dreyfuss G, Matunis MJ, Pinol-Roma S, Burd CG (1993) hnRNP proteins and the biogenesis of mRNA. Annu Rev Biochem 62:289–321PubMedGoogle Scholar
  31. Dulic V, Lees E, Reed SI (1992) Association of human cyclin E with a periodic G1-S phase protein kinase. Science 257:1958–1961PubMedGoogle Scholar
  32. Ellis DJ, Jenkins H, Whitfield WG, Hutchison CJ (1997) GST-lamin fusion proteins act as dominant negative mutants in Xenopus egg extract and reveal the function of the lamina in DNA replication. J Cell Sci 110(Pt 20):2507–2518PubMedGoogle Scholar
  33. Fischer U, Liu Q, Dreyfuss G (1997) The SMN-SIP1 complex has an essential role in spliceosomal snRNP biogenesis. Cell 90:1023–1029PubMedGoogle Scholar
  34. Fox MH, Arndt-Jovin DJ, Jovin TM, Baumann PH, Robert-Nicoud M (1991) Spatial and temporal distribution of DNA replication sites localized by immunofluorescence and confocal microscopy in mouse fibroblasts. J Cell Sci 99(Pt 2):247–253PubMedGoogle Scholar
  35. Goldberg M, Jenkins H, Allen T, Whitfield WG, Hutchison CJ (1995) Xenopus lamin B3 has a direct role in the assembly of a replication competent nucleus: evidence from cell-free egg extracts. J Cell Sci 108(Pt 11):3451–3461PubMedGoogle Scholar
  36. Grande MA, van der Kraan I, van Steensel B, Schul W, de The H, van der Voort HT, de Jong L, van Driel R (1996) PML-containing nuclear bodies: their spatial distribution in relation to other nuclear components. J Cell Biochem 63:280–291PubMedGoogle Scholar
  37. Hassan AB, Cook PR (1993) Visualization of replication sites in unfixed human cells. J Cell Sci 105(Pt 2):541–550PubMedGoogle Scholar
  38. Hassan AB, Errington RJ, White NS, Jackson DA, Cook PR (1994) Replication and transcription sites are colocalized in human cells. J Cell Sci 107(Pt 2):425–434PubMedGoogle Scholar
  39. Hebert MD, Szymczyk PW, Shpargel KB, Matera AG (2001) Coilin forms the bridge between Cajal bodies and SMN, the spinal muscular atrophy protein. Genes Dev 15:2720–2729PubMedGoogle Scholar
  40. Hebert MD, Shpargel KB, Ospina JK, Tucker KE, Matera AG (2002) Coilin methylation regulates nuclear body formation. Dev Cell 3:329–337PubMedGoogle Scholar
  41. Henson JD, Neumann AA, Yeager TR, Reddel RR (2002) Alternative lengthening of telomeres in mammalian cells. Oncogene 21:598–610PubMedGoogle Scholar
  42. Hozak P, Hassan AB, Jackson DA, Cook PR (1993) Visualization of replication factories attached to nucleoskeleton. Cell 73:361–373PubMedGoogle Scholar
  43. Hozak P, Cook PR (1994) Replication factories. Trends Cell Biol 4:48–52PubMedGoogle Scholar
  44. Hozak P, Jackson DA, Cook PR (1994) Replication factories and nuclear bodies: the ultrastructural characterization of replication sites during the cell cycle. J Cell Sci 107(Pt 8):2191–2202PubMedGoogle Scholar
  45. Hozak P, Sasseville AM, Raymond Y, Cook PR (1995) Lamin proteins form an internal nucleoskeleton as well as a peripheral lamina in human cells. J Cell Sci 108(Pt 2):635–644PubMedGoogle Scholar
  46. Hughes TA, Pombo A, McManus J, Hozak P, Jackson DA, Cook PR (1995) On the structure of replication and transcription factories. J Cell Sci Suppl 19:59–65PubMedGoogle Scholar
  47. Humbert C, Usson Y (1992) Eukaryotic DNA replication is a topographically ordered process. Cytometry 13:603–614PubMedGoogle Scholar
  48. Hunter T, Pines J (1994) Cyclins and cancer. II: cyclin D and CDK inhibitors come of age. Cell 79:573–582PubMedGoogle Scholar
  49. Hutchison CJ, Cox R, Drepaul RS, Gomperts M, Ford CC (1987) Periodic DNA synthesis in cell-free extracts of Xenopus eggs. Embo J 6:2003–2010PubMedGoogle Scholar
  50. Ishimi Y (1997) A DNA helicase activity is associated with an MCM4, −6, and −7 protein complex. J Biol Chem 272:24508–24513PubMedGoogle Scholar
  51. Jackson DA, Cook PR (1986) A cell-cycle-dependent DNA polymerase activity that replicates intact DNA in chromatin. J Mol Biol 192:65–76PubMedGoogle Scholar
  52. Jackson DA, Yuan J, Cook PR (1988) A gentle method for preparing cyto- and nucleo-skeletons and associated chromatin. J Cell Sci 90(Pt 3):365–378PubMedGoogle Scholar
  53. Jady BE, Darzacq X, Tucker KE, Matera AG, Bertrand E, Kiss T (2003) Modification of Sm small nuclear RNAs occurs in the nucleoplasmic Cajal body following import from the cytoplasm. Embo J 22:1878–1888PubMedGoogle Scholar
  54. Jensen K, Shiels C, Freemont PS (2001) PML protein isoforms and the RBCC/TRIM motif. Oncogene 20:7223–7233PubMedGoogle Scholar
  55. Jul-Larsen A, Visted T, Karlsen BO, Rinaldo CH, Bjerkvig R, Lonning PE, Boe SO (2004) PML-nuclear bodies accumulate DNA in response to polyomavirus BK and simian virus 40 replication. Exp Cell Res 298:58–73PubMedGoogle Scholar
  56. Kennedy BK, Barbie DA, Classon M, Dyson N, Harlow E (2000) Nuclear organization of DNA replication in primary mammalian cells. Genes Dev 14:2855–2868PubMedGoogle Scholar
  57. Kill IR, Bridger JM, Campbell KH, Maldonado-Codina G, Hutchison CJ (1991) The timing of the formation and usage of replicase clusters in S-phase nuclei of human diploid fibroblasts. J Cell Sci 100(Pt 4):869–876PubMedGoogle Scholar
  58. Koff A, Cross F, Fisher A, Schumacher J, Leguellec K, Philippe M, Roberts JM (1991) Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family. Cell 66:1217–1228PubMedGoogle Scholar
  59. Koff A, Giordano A, Desai D, Yamashita K, Harper JW, Elledge S, Nishimoto T, Morgan DO, Franza BR, Roberts JM (1992) Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle. Science 257:1689–1694PubMedGoogle Scholar
  60. Krecic AM, Swanson MS (1999) hnRNP complexes: composition, structure, and function. Curr Opin Cell Biol 11:363–371PubMedGoogle Scholar
  61. Krishna TS, Kong XP, Gary S, Burgers PM, Kuriyan J (1994) Crystal structure of the eukaryotic DNA polymerase processivity factor PCNA. Cell 79:1233–1243PubMedGoogle Scholar
  62. Lees E, Faha B, Dulic V, Reed SI, Harlow E (1992) Cyclin E/cdk2 and cyclin A/cdk2 kinases associate with p107 and E2F in a temporally distinct manner. Genes Dev 6:1874–1885PubMedGoogle Scholar
  63. Lehner CF, Stick R, Eppenberger HM, Nigg EA (1987) Differential expression of nuclear lamin proteins during chicken development. J Cell Biol 105:577–587PubMedGoogle Scholar
  64. Leonhardt H, Page AW, Weier HU, Bestor TH (1992) A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell 71:865–873PubMedGoogle Scholar
  65. Leonhardt H, Rahn HP, Weinzierl P, Sporbert A, Cremer T, Zink D, Cardoso MC (2000a) Dynamics of DNA replication factories in living cells. J Cell Biol 149:271–280PubMedGoogle Scholar
  66. Leonhardt H, Sporbert A, Cardoso MC (2000b) Targeting regulatory factors to intranuclear replication sites. Crit Rev Eukaryot Gene Expr 10:127–133PubMedGoogle Scholar
  67. Lew DJ, Dulic V, Reed SI (1991) Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast. Cell 66:1197–1206PubMedGoogle Scholar
  68. Li CJ, Vassilev A, DePamphilis ML (2004) Role for Cdk1 (Cdc2)/cyclin A in preventing the mammalian origin recognition complex’s largest subunit (Orc1) from binding to chromatin during mitosis. Mol Cell Biol 24:5875–5886PubMedGoogle Scholar
  69. Manders EM, Stap J, Brakenhoff GJ, van Driel R, Aten JA (1992) Dynamics of three-dimensional replication patterns during the S-phase, analysed by double labelling of DNA and confocal microscopy. J Cell Sci 103(Pt 3):857–862PubMedGoogle Scholar
  70. Maul GG (1998) Nuclear domain 10, the site of DNA virus transcription and replication. Bioessays 20:660–667PubMedGoogle Scholar
  71. Meier J, Campbell KH, Ford CC, Stick R, Hutchison CJ (1991) The role of lamin LIII in nuclear assembly and DNA replication, in cell-free extracts of Xenopus eggs. J Cell Sci 98(Pt 3):271–279PubMedGoogle Scholar
  72. Meier UT, Blobel G (1992) Nopp140 shuttles on tracks between nucleolus and cytoplasm. Cell 70:127–138PubMedGoogle Scholar
  73. Meister G, Eggert C, Fischer U (2002) SMN-mediated assembly of RNPs: a complex story. Trends Cell Biol 12:472–478PubMedGoogle Scholar
  74. Miller ME, Cross FR (2001) Cyclin specificity: how many wheels do you need on a unicycle? J Cell Sci 114:1811–1820PubMedGoogle Scholar
  75. Mills AD, Blow JJ, White JG, Amos WB, Wilcock D, Laskey RA (1989) Replication occurs at discrete foci spaced throughout nuclei replicating in vitro. J Cell Sci 94(Pt 3):471–477PubMedGoogle Scholar
  76. Minshull J, Golsteyn R, Hill CS, Hunt T (1990) The A- and B-type cyclin associated cdc2 kinases in Xenopus turn on and off at different times in the cell cycle. Embo J 9:2865–2875PubMedGoogle Scholar
  77. Moir RD, Montag-Lowy M, Goldman RD (1994) Dynamic properties of nuclear lamins: lamin B is associated with sites of DNA replication. J Cell Biol 125:1201–1212PubMedGoogle Scholar
  78. Moir RD, Spann TP, Herrmann H, Goldman RD (2000) Disruption of nuclear lamin organization blocks the elongation phase of DNA replication. J Cell Biol 149:1179–1192PubMedGoogle Scholar
  79. Moore JD, Kirk JA, Hunt T (2003) Unmasking the S-phase-promoting potential of cyclin B1. Science 300:987–990PubMedGoogle Scholar
  80. Morris L, Allen KE, La Thangue NB (2000) Regulation of E2F transcription by cyclin E-Cdk2 kinase mediated through p300/CBP co-activators. Nat Cell Biol 2:232–239PubMedGoogle Scholar
  81. Nakamura H, Morita T, Sato C (1986) Structural organizations of replicon domains during DNA synthetic phase in the mammalian nucleus. Exp Cell Res 165:291–297PubMedGoogle Scholar
  82. Nakayasu H, Berezney R (1989) Mapping replicational sites in the eucaryotic cell nucleus. J Cell Biol 108:1–11PubMedGoogle Scholar
  83. Newport JW, Wilson KL, Dunphy WG (1990) A lamin-independent pathway for nuclear envelope assembly. J Cell Biol 111:2247–2259PubMedGoogle Scholar
  84. O’Keefe RT, Henderson SC, Spector DL (1992) Dynamic organization of DNA replication in mammalian cell nuclei: spatially and temporally defined replication of chromosome-specific alpha-satellite DNA sequences. J Cell Biol 116:1095–1110PubMedGoogle Scholar
  85. Olins AL, Moyer BA, Kim SH, Allison DP (1989) Synthesis of a more stable osmium ammine electron-dense DNA stain. J Histochem Cytochem 37:395–398PubMedGoogle Scholar
  86. Philimonenko AA, Janacek J, Hozak P (2000) Statistical evaluation of colocalization patterns in immunogold labeling experiments. J Struct Biol 132:201–210PubMedGoogle Scholar
  87. Philimonenko AA, Jackson DA, Hodny Z, Janacek J, Cook PR, Hozak P (2004) Dynamics of DNA replication: an ultrastructural study. J Struct Biol 148:279–289PubMedGoogle Scholar
  88. Pines J, Hunter T (1991) Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transport. J Cell Biol 115:1–17PubMedGoogle Scholar
  89. Pinol-Roma S, Choi YD, Matunis MJ, Dreyfuss G (1988) Immunopurification of heterogeneous nuclear ribonucleoprotein particles reveals an assortment of RNA-binding proteins. Genes Dev 2:215–227PubMedGoogle Scholar
  90. Prosperi E, Scovassi AI, Stivala LA, Bianchi L (1994) Proliferating cell nuclear antigen bound to DNA synthesis sites: phosphorylation and association with cyclin D1 and cyclin A. Exp Cell Res 215:257–262PubMedGoogle Scholar
  91. Quelle DE, Ashmun RA, Shurtleff SA, Kato JY, Bar-Sagi D, Roussel MF, Sherr CJ (1993) Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts. Genes Dev 7:1559–1571PubMedGoogle Scholar
  92. Rao PN (1968) Mitotic synchrony in mammalian cells treated with nitrous oxide at high pressure. Science 160:774–776PubMedGoogle Scholar
  93. Raska I, Andrade LE, Ochs RL, Chan EK, Chang CM, Roos G, Tan EM (1991) Immunological and ultrastructural studies of the nuclear coiled body with autoimmune antibodies. Exp Cell Res 195:27–37PubMedGoogle Scholar
  94. Rattner JB, Hamkalo BA (1979) Nucleosome packing in interphase chromatin. J Cell Biol 81:453–457PubMedGoogle Scholar
  95. Raymond Y, Gagnon G (1988) Lamin B shares a number of distinct epitopes with lamins A and C and with intermediate filament proteins. Biochemistry 27:2590–2597PubMedGoogle Scholar
  96. Reed SI (1997) Control of the G1/S transition. Cancer Surv 29:7–23PubMedGoogle Scholar
  97. Rober RA, Weber K, Osborn M (1989) Differential timing of nuclear lamin A/C expression in the various organs of the mouse embryo and the young animal: a developmental study. Development 105:365–378PubMedGoogle Scholar
  98. Salas M, Miller T J, Leis J, DePamphilis M L (1999) Mechanisms for priming DNA synthesis. In: Concepts in eucaryotic DNA replication. Cold Spring Harbor Laboratory Press, New YorkGoogle Scholar
  99. Sanchez I, Dynlacht BD (2005) New insights into cyclins, CDKs, and cell cycle control. Semin Cell Dev Biol 16:311–321PubMedGoogle Scholar
  100. Saunders WS, Cooke CA, Earnshaw WC (1991) Compartmentalization within the nucleus: discovery of a novel subnuclear region. J Cell Biol 115:919–931PubMedGoogle Scholar
  101. Sherr CJ (1994) G1 phase progression: cycling on cue. Cell 79:551–555PubMedGoogle Scholar
  102. Sherr CJ (1996) Cancer cell cycles. Science 274:1672–1677PubMedGoogle Scholar
  103. Sherwood SW, Rush DF, Kung AL, Schimke RT (1994) Cyclin B1 expression in HeLa S3 cells studied by flow cytometry. Exp Cell Res 211:275–281PubMedGoogle Scholar
  104. Shtivelman E, Bishop JM (1993) The human gene AHNAK encodes a large phosphoprotein located primarily in the nucleus. J Cell Biol 120:625–630PubMedGoogle Scholar
  105. Sobczak-Thepot J, Harper F, Florentin Y, Zindy F, Brechot C, Puvion E (1993) Localization of cyclin A at the sites of cellular DNA replication. Exp Cell Res 206:43–48PubMedGoogle Scholar
  106. Spann TP, Moir RD, Goldman AE, Stick R, Goldman RD (1997) Disruption of nuclear lamin organization alters the distribution of replication factors and inhibits DNA synthesis. J Cell Biol 136:1201–1212PubMedGoogle Scholar
  107. Spector DL (1993) Macromolecular domains within the cell nucleus. Annu Rev Cell Biol 9:265–315PubMedGoogle Scholar
  108. Stuurman N, de Graaf A, Floore A, Josso A, Humbel B, de Jong L, van Driel R (1992) A monoclonal antibody recognizing nuclear matrix-associated nuclear bodies. J Cell Sci 101(Pt 4):773–784PubMedGoogle Scholar
  109. Tucker KE, Berciano MT, Jacobs EY, LePage DF, Shpargel KB, Rossire JJ, Chan EK, Lafarga M, Conlon RA, Matera AG (2001) Residual Cajal bodies in coilin knockout mice fail to recruit Sm snRNPs and SMN, the spinal muscular atrophy gene product. J Cell Biol 154:293–307PubMedGoogle Scholar
  110. Waga S, Stillman B (1998) The DNA replication fork in eukaryotic cells. Annu Rev Biochem 67:721–751PubMedGoogle Scholar
  111. Wolin SL, Cedervall T (2002) The La protein. Annu Rev Biochem 71:375–403PubMedGoogle Scholar
  112. Wuarin J, Schibler U (1994) Physical isolation of nascent RNA chains transcribed by RNA polymerase II: evidence for cotranscriptional splicing. Mol Cell Biol 14:7219–7225PubMedGoogle Scholar
  113. Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D (1993) p21 is a universal inhibitor of cyclin kinases. Nature 366:701–704PubMedGoogle Scholar
  114. Yang J, Bardes ES, Moore JD, Brennan J, Powers MA, Kornbluth S (1998) Control of cyclin B1 localization through regulated binding of the nuclear export factor CRM1. Genes Dev 12:2131–2143PubMedGoogle Scholar
  115. Yu YT, Scharl EC, Smith CM, Steitz J A (1999) The growing world of nuclear ribonucleoproteins. In: Gesteland R F, Cech T R, Atkins JF (Eds) The RNA world. Cold Spring Harbor Lab. Press, Plainview, pp 487–524Google Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Anatoly A. Philimonenko
    • 1
  • Zdeněk Hodný
    • 1
  • Dean A. Jackson
    • 2
  • Pavel Hozák
    • 1
  1. 1.Institute of Experimental MedicineAcademy of Sciences of the Czech RepublicPrague 4-KrčCzech Republic
  2. 2.Faculty of Life Sciences, Jackson’s MillUniversity of Manchester ManchesterUK

Personalised recommendations