The organization of replication and transcription

Science

Volumn 284, Issue 5421, 1999, Pages 1790-1795

  Cook, Peter R ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CELL DNA; DNA POLYMERASE; RNA; RNA POLYMERASE; NUCLEIC ACID;

CELL COMPARTMENTALIZATION; DNA REPLICATION; DNA TRANSCRIPTION; ENZYME ACTIVITY; ENZYME BINDING; ENZYME IMMOBILIZATION; ENZYME MECHANISM; HUMAN; MOLECULAR DYNAMICS; MOLECULAR MODEL; PRIORITY JOURNAL; REACTION ANALYSIS; REVIEW; DNA TEMPLATE; NONHUMAN; POLYMERASE CHAIN REACTION; SEQUENCE HOMOLOGY;

ANIMALS; DNA REPLICATION; DNA-DIRECTED DNA POLYMERASE; DNA-DIRECTED RNA POLYMERASES; HUMANS; MODELS, GENETIC; REPLICATION ORIGIN; TEMPLATES, GENETIC; TRANSCRIPTION, GENETIC;

EID: 0033546210     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.284.5421.1790     Document Type: Review

References (92)

1. B. Alberts et al., Molecular Biology of the Cell (Garland, New York, ed. 3, 1994); H. Lodish et al., Molecular Cell Biology (Scientific American Books, New York, ed. 3, 1995).
2. B. Alberts et al., Molecular Biology of the Cell (Garland, New York, ed. 3, 1994); H. Lodish et al., Molecular Cell Biology (Scientific American Books, New York, ed. 3, 1995).
3. A. Kornberg and T. A. Baker, DNA Replication (Freeman, New York, ed. 3, 1992).
4. Recent evidence suggests that eukaryotic RNA polymerase II [S. M. Uptain, C. M. Kane, M. J. Chamberlin, Annu. Rev. Biochem. 66, 117 (1997)] associates with other factors and "mediators" [V. E. Myers and R. A. Young, J. Biol. Chem. 273, 27757 (1998)] to form a multifunctional holoenzyme involved in transcription, splicing, polyadenylation [S. McCracken et al., Nature 385, 357 (1997)], DNA-remodeling [H. Cho et al., Mol. Cell. Biol. 18, 5355 (1998)], and repair [E. Maldonado et al., Nature 381, 86 (1996); R. Scully et al., Proc. Natl. Acad. Sci. U.S.A. 94, 5605 (1997)].
5. Recent evidence suggests that eukaryotic RNA polymerase II [S. M. Uptain, C. M. Kane, M. J. Chamberlin, Annu. Rev. Biochem. 66, 117 (1997)] associates with other factors and "mediators" [V. E. Myers and R. A. Young, J. Biol. Chem. 273, 27757 (1998)] to form a multifunctional holoenzyme involved in transcription, splicing, polyadenylation [S. McCracken et al., Nature 385, 357 (1997)], DNA-remodeling [H. Cho et al., Mol. Cell. Biol. 18, 5355 (1998)], and repair [E. Maldonado et al., Nature 381, 86 (1996); R. Scully et al., Proc. Natl. Acad. Sci. U.S.A. 94, 5605 (1997)].
6. Recent evidence suggests that eukaryotic RNA polymerase II [S. M. Uptain, C. M. Kane, M. J. Chamberlin, Annu. Rev. Biochem. 66, 117 (1997)] associates with other factors and "mediators" [V. E. Myers and R. A. Young, J. Biol. Chem. 273, 27757 (1998)] to form a multifunctional holoenzyme involved in transcription, splicing, polyadenylation [S. McCracken et al., Nature 385, 357 (1997)], DNA-remodeling [H. Cho et al., Mol. Cell. Biol. 18, 5355 (1998)], and repair [E. Maldonado et al., Nature 381, 86 (1996); R. Scully et al., Proc. Natl. Acad. Sci. U.S.A. 94, 5605 (1997)].
7. Recent evidence suggests that eukaryotic RNA polymerase II [S. M. Uptain, C. M. Kane, M. J. Chamberlin, Annu. Rev. Biochem. 66, 117 (1997)] associates with other factors and "mediators" [V. E. Myers and R. A. Young, J. Biol. Chem. 273, 27757 (1998)] to form a multifunctional holoenzyme involved in transcription, splicing, polyadenylation [S. McCracken et al., Nature 385, 357 (1997)], DNA-remodeling [H. Cho et al., Mol. Cell. Biol. 18, 5355 (1998)], and repair [E. Maldonado et al., Nature 381, 86 (1996); R. Scully et al., Proc. Natl. Acad. Sci. U.S.A. 94, 5605 (1997)].
8. Recent evidence suggests that eukaryotic RNA polymerase II [S. M. Uptain, C. M. Kane, M. J. Chamberlin, Annu. Rev. Biochem. 66, 117 (1997)] associates with other factors and "mediators" [V. E. Myers and R. A. Young, J. Biol. Chem. 273, 27757 (1998)] to form a multifunctional holoenzyme involved in transcription, splicing, polyadenylation [S. McCracken et al., Nature 385, 357 (1997)], DNA-remodeling [H. Cho et al., Mol. Cell. Biol. 18, 5355 (1998)], and repair [E. Maldonado et al., Nature 381, 86 (1996); R. Scully et al., Proc. Natl. Acad. Sci. U.S.A. 94, 5605 (1997)].
9. Recent evidence suggests that eukaryotic RNA polymerase II [S. M. Uptain, C. M. Kane, M. J. Chamberlin, Annu. Rev. Biochem. 66, 117 (1997)] associates with other factors and "mediators" [V. E. Myers and R. A. Young, J. Biol. Chem. 273, 27757 (1998)] to form a multifunctional holoenzyme involved in transcription, splicing, polyadenylation [S. McCracken et al., Nature 385, 357 (1997)], DNA-remodeling [H. Cho et al., Mol. Cell. Biol. 18, 5355 (1998)], and repair [E. Maldonado et al., Nature 381, 86 (1996); R. Scully et al., Proc. Natl. Acad. Sci. U.S.A. 94, 5605 (1997)].
10. S. Waga and B. Stillman, Annu. Rev. Biochem. 67, 721 (1998).
11. The general term "substructure" is used here because so tittle is known about the molecular contents of candidate skeletons in bacteria or higher cells [R. Berezney and D. S. Coffey, J. Cell Biol. 73, 616 (1977); T. Pederson, J. Mol. Biol. 277, 147 (1998); (8)].
12. The general term "substructure" is used here because so tittle is known about the molecular contents of candidate skeletons in bacteria or higher cells [R. Berezney and D. S. Coffey, J. Cell Biol. 73, 616 (1977); T. Pederson, J. Mol. Biol. 277, 147 (1998); (8)].
13. DNA-dependent DNA polymerases (for example, the bacterial polymerase I and human polymerase α), DNA-dependent RNA polymerases, retroviral reverse transcriptases, and RNA-dependent RNA polymerases share characteristic sequences [P. Argos, Nucleic Acids Res. 16, 9909 (1988); D. K. Braithwaite and J. Ito, ibid. 21, 787 (1993)]. The polymerizing domain of the Klenow fragment of bacterial DNA polymerase I, reverse transcriptase, and the T7 RNA polymerase also have extensive structural homology [C. M. Joyce and T. A. Steitz, Annu. Rev. Biochem. 63, 777 (1994)], as do the processivity factors of bacterial and mammalian DNA polymerases [X.-P. Kong, R. Onrust, M. O'Donnell, J. Kuriyan, Cell 69, 425 (1992)].
14. DNA-dependent DNA polymerases (for example, the bacterial polymerase I and human polymerase α), DNA-dependent RNA polymerases, retroviral reverse transcriptases, and RNA-dependent RNA polymerases share characteristic sequences [P. Argos, Nucleic Acids Res. 16, 9909 (1988); D. K. Braithwaite and J. Ito, ibid. 21, 787 (1993)]. The polymerizing domain of the Klenow fragment of bacterial DNA polymerase I, reverse transcriptase, and the T7 RNA polymerase also have extensive structural homology [C. M. Joyce and T. A. Steitz, Annu. Rev. Biochem. 63, 777 (1994)], as do the processivity factors of bacterial and mammalian DNA polymerases [X.-P. Kong, R. Onrust, M. O'Donnell, J. Kuriyan, Cell 69, 425 (1992)].
15. DNA-dependent DNA polymerases (for example, the bacterial polymerase I and human polymerase α), DNA-dependent RNA polymerases, retroviral reverse transcriptases, and RNA-dependent RNA polymerases share characteristic sequences [P. Argos, Nucleic Acids Res. 16, 9909 (1988); D. K. Braithwaite and J. Ito, ibid. 21, 787 (1993)]. The polymerizing domain of the Klenow fragment of bacterial DNA polymerase I, reverse transcriptase, and the T7 RNA polymerase also have extensive structural homology [C. M. Joyce and T. A. Steitz, Annu. Rev. Biochem. 63, 777 (1994)], as do the processivity factors of bacterial and mammalian DNA polymerases [X.-P. Kong, R. Onrust, M. O'Donnell, J. Kuriyan, Cell 69, 425 (1992)].
16. DNA-dependent DNA polymerases (for example, the bacterial polymerase I and human polymerase α), DNA-dependent RNA polymerases, retroviral reverse transcriptases, and RNA-dependent RNA polymerases share characteristic sequences [P. Argos, Nucleic Acids Res. 16, 9909 (1988); D. K. Braithwaite and J. Ito, ibid. 21, 787 (1993)]. The polymerizing domain of the Klenow fragment of bacterial DNA polymerase I, reverse transcriptase, and the T7 RNA polymerase also have extensive structural homology [C. M. Joyce and T. A. Steitz, Annu. Rev. Biochem. 63, 777 (1994)], as do the processivity factors of bacterial and mammalian DNA polymerases [X.-P. Kong, R. Onrust, M. O'Donnell, J. Kuriyan, Cell 69, 425 (1992)].
17. F. Jacob, S. Brenner, F. Cuzin, Cold Spring Harbor Symp. Quant. Biol. 28, 329 (1963).
18. C. D. Webb et al., Cell 88, 667 (1997); M. E. Sharpe and J. Errington, Trends Genet. 15, 70 (1999).
19. C. D. Webb et al., Cell 88, 667 (1997); M. E. Sharpe and J. Errington, Trends Genet. 15, 70 (1999).
20. G. B. Ogden, M. J. Pratt, M. Schaechter, Cell 54, 127 (1988); A. Landouisi, A. Malki, R. Kern, M. Kohiyama, P. Hughes, ibid. 63, 1053 (1990).
21. G. B. Ogden, M. J. Pratt, M. Schaechter, Cell 54, 127 (1988); A. Landouisi, A. Malki, R. Kern, M. Kohiyama, P. Hughes, ibid. 63, 1053 (1990).
22. R. Berezney and D. S. Coffey, Science 189, 291 (1975); S. J. McCready, J. Godwin, D. W. Mason, I. A. Brazell, P. R. Cook, J. Cell Sci. 46, 365 (1980); D. M. Pardoll, B. Vogelstein, D. S. Coffey, Cell 19, 527 (1980).
23. R. Berezney and D. S. Coffey, Science 189, 291 (1975); S. J. McCready, J. Godwin, D. W. Mason, I. A. Brazell, P. R. Cook, J. Cell Sci. 46, 365 (1980); D. M. Pardoll, B. Vogelstein, D. S. Coffey, Cell 19, 527 (1980).
24. R. Berezney and D. S. Coffey, Science 189, 291 (1975); S. J. McCready, J. Godwin, D. W. Mason, I. A. Brazell, P. R. Cook, J. Cell Sci. 46, 365 (1980); D. M. Pardoll, B. Vogelstein, D. S. Coffey, Cell 19, 527 (1980).
25. P. R. Cook, J. Cell Sci. 90, 1 (1988).
26. R. Wessel, J. Schweizer, H. Stahl, J. Virol. 66, 804 (1992).
27. S. C. West, Annu. Rev. Genet. 31, 213 (1997).
28. J. A. Huberman and A. D. Riggs, J. Mol. Biol. 75, 327 (1968).
29. D. A. Jackson and A. Pombo, J. Cell Boil. 140, 1285 (1998).
30. D. A. Jackson and P. R. Cook, EMBO J. 5, 1403 (1986).
31. H. Nakamura, T. Morita, C. Sato, Exp. Cell Res. 165, 291 (1986).
32. H. Nakayasu and R. Berezney, J. Cell Biol. 108, 1 (1989).
33. J. Newport and H. Yan, Curr. Opin. Cell Biol. 8, 365 (1995).
34. A. B. Hassan and P. R. Cook. J. Cell Sci. 105, 541 (1993); E. M. M. Manders, H. Kimura, P. R. Cook, J. Cell Biol. 144, 813 (1998).
35. A. B. Hassan and P. R. Cook. J. Cell Sci. 105, 541 (1993); E. M. M. Manders, H. Kimura, P. R. Cook, J. Cell Biol. 144, 813 (1998).
36. P. Hozák, A. B. Hassan, D. A. Jackson, P. R. Cook, Cell 73, 361 (1993).
37. R. A. Tubo and R. Berezney, J. Biol. Chem. 262, 5857 (1987).
38. K. P. Lemon and A. D. Grossman, Science 282, 1516 (1998).
39. V. C. Culotta, R. Wides, B. Sollner-Webb, Mol. Cell. Biol. 5. 1582 (1985).
40. O. L. Miller and A. H. Bakken, Acta Endocrinol. Suppl. 168, 155 (1972).
41. D. A. Jackson, S. J. McCready, P. R. Cook, Nature 292, 552 (1981).
42. D. A. Jackson and P. R. Cook, EMBO J. 4, 919 (1985); J. Cell Sci. 105, 1143 (1993); P. Dickinson, P. R. Cook, D. A. Jackson, EMBO J. 9, 2207 (1990); D. A. Jackson, J. Bartlett, P. R. Cook, Nucleic Acids Res. 24, 1212 (1996).
43. D. A. Jackson and P. R. Cook, EMBO J. 4, 919 (1985); J. Cell Sci. 105, 1143 (1993); P. Dickinson, P. R. Cook, D. A. Jackson, EMBO J. 9, 2207 (1990); D. A. Jackson, J. Bartlett, P. R. Cook, Nucleic Acids Res. 24, 1212 (1996).
44. D. A. Jackson and P. R. Cook, EMBO J. 4, 919 (1985); J. Cell Sci. 105, 1143 (1993); P. Dickinson, P. R. Cook, D. A. Jackson, EMBO J. 9, 2207 (1990); D. A. Jackson, J. Bartlett, P. R. Cook, Nucleic Acids Res. 24, 1212 (1996).
45. D. A. Jackson and P. R. Cook, EMBO J. 4, 919 (1985); J. Cell Sci. 105, 1143 (1993); P. Dickinson, P. R. Cook, D. A. Jackson, EMBO J. 9, 2207 (1990); D. A. Jackson, J. Bartlett, P. R. Cook, Nucleic Acids Res. 24, 1212 (1996).
46. D. A. Jackson, A. B. Hassan, R. J. Errington, P. R. Cook, EMBO J. 12, 1059 (1993).
47. P. R. Cook and F. Gove, Nucleic Acids Res. 20, 3591 (1992).
48. L. F. Liu and J. C. Wang, Proc. Natt. Acad. Sci. U.S.A. 84, 7024 (1987).
49. D.G. Wansink et al., J. Cell Biol. 122, 283 (1993); F. S. Fay, K. L. Taneja, S. Shenoy, L. Lifshitz, R. H. Singer, Exp. Cell Res. 231, 27 (1997).
50. D.G. Wansink et al., J. Cell Biol. 122, 283 (1993); F. S. Fay, K. L. Taneja, S. Shenoy, L. Lifshitz, R. H. Singer, Exp. Cell Res. 231, 27 (1997).
51. F. J. Iborra, A. Pombo, D. A. Jackson, P. R. Cook, J. Cell Sci. 109, 1427 (1996).
52. A. Pombo et al., EMBO J. 18, 2241 (1999).
53. P. J. Shaw and E. G. Jordan, Annu. Rev. Cell Dev. Biol. 11, 93 (1995).
54. D. A. Jackson, F. J. Iborra, E. M. M. Manders, P. R. Cook, Mol. Biol. Cell 9, 1523 (1998).
55. P. Hozák, P. R. Cook, C. Schöfer, W. Mosgöller, F. Wachtler, J. Cell Sci. 107, 639 (1994).
56. These values apply to a HeLa cell under specific growth conditions. However, increasing activity results in an increase both in the number of active transcription units and the number of fibrillar centers [T. Haaf, D. L. Hayman, M. Schmid, Exp. Cell Res. 193, 78 (1991)]. Fragmenting a fibrillar center increases the surface area, and thus, the number of exposed polymerases is increased.
57. T. O'Brien and J. T. Lis, Mol. Cell. Biol. 11, 5285 (1991); A. M. Femino, F. S. Fay, K. Fogarty, R. H. Singer, Science 280, 585 (1998).
58. T. O'Brien and J. T. Lis, Mol. Cell. Biol. 11, 5285 (1991); A. M. Femino, F. S. Fay, K. Fogarty, R. H. Singer, Science 280, 585 (1998).
59. C. D. Laird and W. Y. Chooi, Chromosoma 58, 193 (1976); S. L. McKnight and O. L Miller, Cell 17, 551 (1979); S. Fakan, G. Leser, T. E. Martin, J. Cell Biol. 103, 1153 (1986).
60. C. D. Laird and W. Y. Chooi, Chromosoma 58, 193 (1976); S. L. McKnight and O. L Miller, Cell 17, 551 (1979); S. Fakan, G. Leser, T. E. Martin, J. Cell Biol. 103, 1153 (1986).
61. C. D. Laird and W. Y. Chooi, Chromosoma 58, 193 (1976); S. L. McKnight and O. L Miller, Cell 17, 551 (1979); S. Fakan, G. Leser, T. E. Martin, J. Cell Biol. 103, 1153 (1986).
62. D. J. Wolgemuth and M.-T. Hsu, J. Mol. Biol. 147, 247 (1981); A. L. Beyer, A. H. Bouton, L. O. Hodge, O. L. Miller, ibid., p. 269.
63. D. J. Wolgemuth and M.-T. Hsu, J. Mol. Biol. 147, 247 (1981); A. L. Beyer, A. H. Bouton, L. O. Hodge, O. L. Miller, ibid., p. 269.
64. D. C. Wansink, O. C. Sibon, F. F. M. Cremers, R. van Driel, L. de Jong, J. Cell. Biochem. 62, 10 (1996).
65. F. J. Iborra, D. A. Jackson, P. R. Cook, J. Cell Sci. 111, 2269 (1998).
66. Recent estimates with HeLa cells place 8 to 15 and ∼5 different transcription units in sites dedicated to transcription by polymerases II and III, respectively (33, 35).
67. D. A. Schafer, J. Gelles, M. P. Sheetz, R. Landick, Nature 352, 444 (1991).
68. H. Yin et al.. Science 270, 1653 (1995); J. Gelles and R. Landick, Cell 93, 13 (1998).
69. H. Yin et al.. Science 270, 1653 (1995); J. Gelles and R. Landick, Cell 93, 13 (1998).
70. A. Noy, D. V. Vezenov, J. F. Kayyem, T. J. Meade, C. M. Lieber, Chem. Biol. 4, 519 (1997); M. D. Wang, H. Yin, R. Landick, J. Gelles, S. M. Block, Biophys. J. 72, 1335 (1997).
71. A. Noy, D. V. Vezenov, J. F. Kayyem, T. J. Meade, C. M. Lieber, Chem. Biol. 4, 519 (1997); M. D. Wang, H. Yin, R. Landick, J. Gelles, S. M. Block, Biophys. J. 72, 1335 (1997).
72. The machinery involved in mitochondrial DNA and RNA synthesis [S. Kawano and T. Kuroiwa, Exp. Cell Res. 161, 460 (1985); M. Echeverria, D. Robert, J. P. Carde, S. Litvak, Plant Mol. Biol. 16, 301 (1991)], recombination [V. P. Dave, M. J. Modak, V. N. Pandey, Biochemistry 30, 4763 (1991); T. Haaf, E. I. Golub, G. Reddy, C. M. Radding, D. C. Ward, Proc. Natl. Acad. Sci. U.S.A. 92, 2298 (1995); R. Scully et al., Cell 88, 265 (1997); S. Tashiro et al., Oncogene 12, 2165 (1996)], and the repair of DNA damage [S. J. McCready and P. R. Cook, J. Cell Sci. 70, 189 (1984); D. A. Jackson, A. S. Balajee, L. Mullenders, P. R. Cook, ibid. 107, 1745 (1994); D. A. Jackson, A. B. Hassan, R. J. Errington, P. R. Cook, ibid., p. 1753] has been shown to be associated with underlying structures or concentrated in foci or both.
73. The machinery involved in mitochondrial DNA and RNA synthesis [S. Kawano and T. Kuroiwa, Exp. Cell Res. 161, 460 (1985); M. Echeverria, D. Robert, J. P. Carde, S. Litvak, Plant Mol. Biol. 16, 301 (1991)], recombination [V. P. Dave, M. J. Modak, V. N. Pandey, Biochemistry 30, 4763 (1991); T. Haaf, E. I. Golub, G. Reddy, C. M. Radding, D. C. Ward, Proc. Natl. Acad. Sci. U.S.A. 92, 2298 (1995); R. Scully et al., Cell 88, 265 (1997); S. Tashiro et al., Oncogene 12, 2165 (1996)], and the repair of DNA damage [S. J. McCready and P. R. Cook, J. Cell Sci. 70, 189 (1984); D. A. Jackson, A. S. Balajee, L. Mullenders, P. R. Cook, ibid. 107, 1745 (1994); D. A. Jackson, A. B. Hassan, R. J. Errington, P. R. Cook, ibid., p. 1753] has been shown to be associated with underlying structures or concentrated in foci or both.
74. The machinery involved in mitochondrial DNA and RNA synthesis [S. Kawano and T. Kuroiwa, Exp. Cell Res. 161, 460 (1985); M. Echeverria, D. Robert, J. P. Carde, S. Litvak, Plant Mol. Biol. 16, 301 (1991)], recombination [V. P. Dave, M. J. Modak, V. N. Pandey, Biochemistry 30, 4763 (1991); T. Haaf, E. I. Golub, G. Reddy, C. M. Radding, D. C. Ward, Proc. Natl. Acad. Sci. U.S.A. 92, 2298 (1995); R. Scully et al., Cell 88, 265 (1997); S. Tashiro et al., Oncogene 12, 2165 (1996)], and the repair of DNA damage [S. J. McCready and P. R. Cook, J. Cell Sci. 70, 189 (1984); D. A. Jackson, A. S. Balajee, L. Mullenders, P. R. Cook, ibid. 107, 1745 (1994); D. A. Jackson, A. B. Hassan, R. J. Errington, P. R. Cook, ibid., p. 1753] has been shown to be associated with underlying structures or concentrated in foci or both.
75. The machinery involved in mitochondrial DNA and RNA synthesis [S. Kawano and T. Kuroiwa, Exp. Cell Res. 161, 460 (1985); M. Echeverria, D. Robert, J. P. Carde, S. Litvak, Plant Mol. Biol. 16, 301 (1991)], recombination [V. P. Dave, M. J. Modak, V. N. Pandey, Biochemistry 30, 4763 (1991); T. Haaf, E. I. Golub, G. Reddy, C. M. Radding, D. C. Ward, Proc. Natl. Acad. Sci. U.S.A. 92, 2298 (1995); R. Scully et al., Cell 88, 265 (1997); S. Tashiro et al., Oncogene 12, 2165 (1996)], and the repair of DNA damage [S. J. McCready and P. R. Cook, J. Cell Sci. 70, 189 (1984); D. A. Jackson, A. S. Balajee, L. Mullenders, P. R. Cook, ibid. 107, 1745 (1994); D. A. Jackson, A. B. Hassan, R. J. Errington, P. R. Cook, ibid., p. 1753] has been shown to be associated with underlying structures or concentrated in foci or both.
76. The machinery involved in mitochondrial DNA and RNA synthesis [S. Kawano and T. Kuroiwa, Exp. Cell Res. 161, 460 (1985); M. Echeverria, D. Robert, J. P. Carde, S. Litvak, Plant Mol. Biol. 16, 301 (1991)], recombination [V. P. Dave, M. J. Modak, V. N. Pandey, Biochemistry 30, 4763 (1991); T. Haaf, E. I. Golub, G. Reddy, C. M. Radding, D. C. Ward, Proc. Natl. Acad. Sci. U.S.A. 92, 2298 (1995); R. Scully et al., Cell 88, 265 (1997); S. Tashiro et al., Oncogene 12, 2165 (1996)], and the repair of DNA damage [S. J. McCready and P. R. Cook, J. Cell Sci. 70, 189 (1984); D. A. Jackson, A. S. Balajee, L. Mullenders, P. R. Cook, ibid. 107, 1745 (1994); D. A. Jackson, A. B. Hassan, R. J. Errington, P. R. Cook, ibid., p. 1753] has been shown to be associated with underlying structures or concentrated in foci or both.
77. The machinery involved in mitochondrial DNA and RNA synthesis [S. Kawano and T. Kuroiwa, Exp. Cell Res. 161, 460 (1985); M. Echeverria, D. Robert, J. P. Carde, S. Litvak, Plant Mol. Biol. 16, 301 (1991)], recombination [V. P. Dave, M. J. Modak, V. N. Pandey, Biochemistry 30, 4763 (1991); T. Haaf, E. I. Golub, G. Reddy, C. M. Radding, D. C. Ward, Proc. Natl. Acad. Sci. U.S.A. 92, 2298 (1995); R. Scully et al., Cell 88, 265 (1997); S. Tashiro et al., Oncogene 12, 2165 (1996)], and the repair of DNA damage [S. J. McCready and P. R. Cook, J. Cell Sci. 70, 189 (1984); D. A. Jackson, A. S. Balajee, L. Mullenders, P. R. Cook, ibid. 107, 1745 (1994); D. A. Jackson, A. B. Hassan, R. J. Errington, P. R. Cook, ibid., p. 1753] has been shown to be associated with underlying structures or concentrated in foci or both.
78. The machinery involved in mitochondrial DNA and RNA synthesis [S. Kawano and T. Kuroiwa, Exp. Cell Res. 161, 460 (1985); M. Echeverria, D. Robert, J. P. Carde, S. Litvak, Plant Mol. Biol. 16, 301 (1991)], recombination [V. P. Dave, M. J. Modak, V. N. Pandey, Biochemistry 30, 4763 (1991); T. Haaf, E. I. Golub, G. Reddy, C. M. Radding, D. C. Ward, Proc. Natl. Acad. Sci. U.S.A. 92, 2298 (1995); R. Scully et al., Cell 88, 265 (1997); S. Tashiro et al., Oncogene 12, 2165 (1996)], and the repair of DNA damage [S. J. McCready and P. R. Cook, J. Cell Sci. 70, 189 (1984); D. A. Jackson, A. S. Balajee, L. Mullenders, P. R. Cook, ibid. 107, 1745 (1994); D. A. Jackson, A. B. Hassan, R. J. Errington, P. R. Cook, ibid., p. 1753] has been shown to be associated with underlying structures or concentrated in foci or both.
79. The machinery involved in mitochondrial DNA and RNA synthesis [S. Kawano and T. Kuroiwa, Exp. Cell Res. 161, 460 (1985); M. Echeverria, D. Robert, J. P. Carde, S. Litvak, Plant Mol. Biol. 16, 301 (1991)], recombination [V. P. Dave, M. J. Modak, V. N. Pandey, Biochemistry 30, 4763 (1991); T. Haaf, E. I. Golub, G. Reddy, C. M. Radding, D. C. Ward, Proc. Natl. Acad. Sci. U.S.A. 92, 2298 (1995); R. Scully et al., Cell 88, 265 (1997); S. Tashiro et al., Oncogene 12, 2165 (1996)], and the repair of DNA damage [S. J. McCready and P. R. Cook, J. Cell Sci. 70, 189 (1984); D. A. Jackson, A. S. Balajee, L. Mullenders, P. R. Cook, ibid. 107, 1745 (1994); D. A. Jackson, A. B. Hassan, R. J. Errington, P. R. Cook, ibid., p. 1753] has been shown to be associated with underlying structures or concentrated in foci or both.
80. The machinery involved in mitochondrial DNA and RNA synthesis [S. Kawano and T. Kuroiwa, Exp. Cell Res. 161, 460 (1985); M. Echeverria, D. Robert, J. P. Carde, S. Litvak, Plant Mol. Biol. 16, 301 (1991)], recombination [V. P. Dave, M. J. Modak, V. N. Pandey, Biochemistry 30, 4763 (1991); T. Haaf, E. I. Golub, G. Reddy, C. M. Radding, D. C. Ward, Proc. Natl. Acad. Sci. U.S.A. 92, 2298 (1995); R. Scully et al., Cell 88, 265 (1997); S. Tashiro et al., Oncogene 12, 2165 (1996)], and the repair of DNA damage [S. J. McCready and P. R. Cook, J. Cell Sci. 70, 189 (1984); D. A. Jackson, A. S. Balajee, L. Mullenders, P. R. Cook, ibid. 107, 1745 (1994); D. A. Jackson, A. B. Hassan, R. J. Errington, P. R. Cook, ibid., p. 1753] has been shown to be associated with underlying structures or concentrated in foci or both.
81. B. V. V. Prasad et al. Nature 382, 471 (1996).
82. P. R. Cook, Cell 66, 627 (1991); P. Hozák, D. A. Jackson, P. R. Cook, in Eukaryotic DNA Replication: Frontiers in Molecular Biology, J. J. Blow, Ed. (Oxford Univ. Press, Oxford, 1996), pp, 124-142; F. J. Iborra, A. Pombo, J. McManus, D. A. Jackson, P. R. Cook, Exp. Cell Res. 229, 167 (1996); P. R. Cook, J. Gen. Virol. 74, 691 (1993).
83. P. R. Cook, Cell 66, 627 (1991); P. Hozák, D. A. Jackson, P. R. Cook, in Eukaryotic DNA Replication: Frontiers in Molecular Biology, J. J. Blow, Ed. (Oxford Univ. Press, Oxford, 1996), pp, 124-142; F. J. Iborra, A. Pombo, J. McManus, D. A. Jackson, P. R. Cook, Exp. Cell Res. 229, 167 (1996); P. R. Cook, J. Gen. Virol. 74, 691 (1993).
84. P. R. Cook, Cell 66, 627 (1991); P. Hozák, D. A. Jackson, P. R. Cook, in Eukaryotic DNA Replication: Frontiers in Molecular Biology, J. J. Blow, Ed. (Oxford Univ. Press, Oxford, 1996), pp, 124-142; F. J. Iborra, A. Pombo, J. McManus, D. A. Jackson, P. R. Cook, Exp. Cell Res. 229, 167 (1996); P. R. Cook, J. Gen. Virol. 74, 691 (1993).
85. P. R. Cook, Cell 66, 627 (1991); P. Hozák, D. A. Jackson, P. R. Cook, in Eukaryotic DNA Replication: Frontiers in Molecular Biology, J. J. Blow, Ed. (Oxford Univ. Press, Oxford, 1996), pp, 124-142; F. J. Iborra, A. Pombo, J. McManus, D. A. Jackson, P. R. Cook, Exp. Cell Res. 229, 167 (1996); P. R. Cook, J. Gen. Virol. 74, 691 (1993).
86. A. Pombo et al., EMBO J. 17, 1768 (1998).
87. The bacterial genome may be organized as in Fig. 5, with a "cloud" of loops surrounding a loose polymerase core [D. E. Pettijohn and R. Hecht, Cold Spring Harbor Symp. Quant. Biol. 38, 31 (1973); S. Krawiec and M. Riley, Microbiol. Rev. 54, 502 (1990)]. The RNA polymerase may also have a ribosome-binding site so that a new protein is made as a transcript is extruded through an attached ribosome. Then, the distance between active sites in the polymerase and ribosome must accommodate RNA loops that allow transcriptional termination and attenuation [C. Yanofsky, Nature 289, 751 (1981)].
88. The bacterial genome may be organized as in Fig. 5, with a "cloud" of loops surrounding a loose polymerase core [D. E. Pettijohn and R. Hecht, Cold Spring Harbor Symp. Quant. Biol. 38, 31 (1973); S. Krawiec and M. Riley, Microbiol. Rev. 54, 502 (1990)]. The RNA polymerase may also have a ribosome-binding site so that a new protein is made as a transcript is extruded through an attached ribosome. Then, the distance between active sites in the polymerase and ribosome must accommodate RNA loops that allow transcriptional termination and attenuation [C. Yanofsky, Nature 289, 751 (1981)].
89. The bacterial genome may be organized as in Fig. 5, with a "cloud" of loops surrounding a loose polymerase core [D. E. Pettijohn and R. Hecht, Cold Spring Harbor Symp. Quant. Biol. 38, 31 (1973); S. Krawiec and M. Riley, Microbiol. Rev. 54, 502 (1990)]. The RNA polymerase may also have a ribosome-binding site so that a new protein is made as a transcript is extruded through an attached ribosome. Then, the distance between active sites in the polymerase and ribosome must accommodate RNA loops that allow transcriptional termination and attenuation [C. Yanofsky, Nature 289, 751 (1981)].
90. P. R. Cook, J. Cell Sci. 108, 2927 (1995); ibid. 110, 1033 (1997).
91. P. R. Cook, J. Cell Sci. 108, 2927 (1995); ibid. 110, 1033 (1997).
92. I thank the Cancer Research Campaign and the Wellcome Trust for support and A. Pombo and D. Jackson for providing figures.