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Regulation of S Phase

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Cell Cycle Regulation

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 42))

Abstract

Regulation of DNA replication is critical for accurate and timely dissemination of genomic material to daughter cells. The cell uses a variety of mechanisms to control this aspect of the cell cycle. There are various determinants of origin identification, as well as a large number of proteins required to load replication complexes at these defined genomic regions. A pre-Replication Complex (pre-RC) associates with origins in the G1 phase. This complex includes the Origin Recognition Complex (ORC), which serves to recognize origins, the putative helicase MCM2-7, and other factors important for complex assembly. Following pre-RC loading, a pre-Initiation Complex (pre-IC) builds upon the helicase with factors required for eventual loading of replicative polymerases. The chromatin association of these two complexes is temporally distinct, with pre-RC being inhibited, and pre-IC being activated by cyclin-dependent kinases (Cdks). This regulation is the basis for replication licensing, which allows replication to occur at a specific time once, and only once, per cell cycle. By preventing extra rounds of replication within a cell cycle, or by ensuring the cell cycle cannot progress until the environmental and intracellular conditions are most optimal, cells are able to carry out a successful replication cycle with minimal mutations.

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References

  1. Adachi Y, Usukura J, Yanagida M (1997) A globular complex formation by Nda1 and the other five members of the MCM protein family in fission yeast. Genes Cells 2:467–479

    PubMed  CAS  Google Scholar 

  2. Aggarwal BD, Calvi BR (2004) Chromatin regulates origin activity in Drosophila follicle cells. Nature 430:372–376

    PubMed  CAS  Google Scholar 

  3. Aladjem MI, Rodewald LW, Kolman JL, Wahl GM (1998) Genetic dissection of a mammalian replicator in the human beta-globin locus. Science 281:1005–1009

    PubMed  CAS  Google Scholar 

  4. Alexandrow MG, Hamlin JL (2004) Cdc6 chromatin affinity is unaffected by serine-54 phosphorylation, S-phase progression, and overexpression of cyclin A. Mol Cell Biol 24:1614–1627

    PubMed  CAS  Google Scholar 

  5. Altman AL, Fanning E (2004) Defined sequence modules and an architectural element cooperate to promote initiation at an ectopic mammalian chromosomal replication origin. Mol Cell Biol 24:4138–4150

    PubMed  CAS  Google Scholar 

  6. Aparicio OM, Weinstein DM, Bell SP (1997) Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase. Cell 91:59–69

    PubMed  CAS  Google Scholar 

  7. Araki H, Leem SH, Phongdara A, Sugino A (1995) Dpb11, which interacts with DNA polymerase II(epsilon) in Saccharomyces cerevisiae, has a dual role in S-phase progression and at a cell cycle checkpoint. Proc Natl Acad Sci USA 92:11791–11795

    PubMed  CAS  Google Scholar 

  8. Araki M, Wharton RP, Tang Z, Yu H, Asano M (2003) Degradation of origin recognition complex large subunit by the anaphase-promoting complex in Drosophila. Embo J 22:6115–6126

    PubMed  CAS  Google Scholar 

  9. Arentson E, Faloon P, Seo J, Moon E, Studts JM, Fremont DH, Choi K (2002) Oncogenic potential of the DNA replication licensing protein CDT1. Oncogene 21:1150–1158

    PubMed  CAS  Google Scholar 

  10. Arias EE, Walter JC (2005) Replication-dependent destruction of Cdt1 limits DNA replication to a single round per cell cycle in Xenopus egg extracts. Genes Dev 19:114–126

    CAS  Google Scholar 

  11. Aves SJ, Tongue N, Foster AJ, Hart EA (1998) The essential schizosaccharomyces pombe cdc23 DNA replication gene shares structural and functional homology with the Saccharomyces cerevisiae DNA43 (MCM10) gene. Curr Genet 34:164–171

    PubMed  CAS  Google Scholar 

  12. Bell SP, Stillman B (1992) ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex. Nature 357:128–134

    PubMed  CAS  Google Scholar 

  13. Bell SP, Dutta A (2002) DNA replication in eukaryotic cells. Annu Rev Biochem 71:333–374

    PubMed  CAS  Google Scholar 

  14. Biermann E, Baack M, Kreitz S, Knippers R (2002) Synthesis and turn-over of the replicative Cdc6 protein during the HeLa cell cycle. Eur J Biochem 269:1040–1046

    PubMed  CAS  Google Scholar 

  15. Blanchard F, Rusiniak ME, Sharma K, Sun X, Todorov I, Castellano MM, Gutierrez C, Baumann H, Burhans WC (2002) Targeted destruction of DNA replication protein Cdc6 by cell death pathways in mammals and yeast. Mol Biol Cell 13:1536–1549

    PubMed  CAS  Google Scholar 

  16. Blow JJ, Laskey RA (1988) A role for the nuclear envelope in controlling DNA replication within the cell cycle. Nature 332:546–548

    PubMed  CAS  Google Scholar 

  17. Bousset K, Diffley JF (1998). The Cdc7 protein kinase is required for origin firing during S phase. Genes Dev 12:480–490

    CAS  Google Scholar 

  18. Boyd JB, Golino MD, Nguyen TD, Green MM (1976) Isolation and characterization of X-linked mutants of Drosophila melanogaster which are sensitive to mutagens. Genetics 84:485–506

    PubMed  CAS  Google Scholar 

  19. Brown GW, Kelly TJ (1999) Cell cycle regulation of Dfp1, an activator of the Hsk1 protein kinase. Proc Natl Acad Sci USA 96:8443–8448

    PubMed  CAS  Google Scholar 

  20. Burhans WC, Vassilev LT, Caddle MS, Heintz NH, DePamphilis ML (1990) Identification of an origin of bidirectional DNA replication in mammalian chromosomes. Cell 62:955–965

    PubMed  CAS  Google Scholar 

  21. Carpenter PB, Mueller PR, Dunphy WG (1996) Role for a Xenopus Orc2-related protein in controlling DNA replication. Nature 379:357–360

    PubMed  CAS  Google Scholar 

  22. Chapman JW, Johnston LH (1989) The yeast gene, DBF4, essential for entry into S phase is cell cycle regulated. Exp Cell Res 180:419–428

    PubMed  CAS  Google Scholar 

  23. Chaudhuri B, Xu H, Todorov I, Dutta A, Yates JL (2001) Human DNA replication initiation factors, ORC and MCM, associate with oriP of Epstein-Barr virus. Proc Natl Acad Sci USA 98:10085–10089

    PubMed  CAS  Google Scholar 

  24. Chesnokov I, Remus D, Botchan M (2001) Functional analysis of mutant and wild-type Drosophila origin recognition complex. Proc Natl Acad Sci USA 98:11997–12002

    PubMed  CAS  Google Scholar 

  25. Chesnokov I, Gossen M, Remus D, Botchan M (1999) Assembly of functionally active Drosophila origin recognition complex from recombinant proteins. Genes Dev 13:1289–1296

    PubMed  CAS  Google Scholar 

  26. Chong JP, Mahbubani HM, Khoo CY, Blow JJ (1995) Purification of an MCM-containing complex as a component of the DNA replication licensing system. Nature 375:418–421

    PubMed  CAS  Google Scholar 

  27. Chong JP, Hayashi MK, Simon MN, Xu RM, Stillman B (2000) A double-hexamer archaeal minichromosome maintenance protein is an ATP-dependent DNA helicase. Proc Natl Acad Sci USA 97:1530–1535

    PubMed  CAS  Google Scholar 

  28. Cocker JH, Piatti S, Santocanale C, Nasmyth K, Diffley JF (1996) An essential role for the Cdc6 protein in forming the pre-replicative complexes of budding yeast. Nature 379:180–182

    PubMed  CAS  Google Scholar 

  29. Coleman TR, Carpenter PB, Dunphy WG (1996) The Xenopus Cdc6 protein is essential for the initiation of a single round of DNA replication in cell-free extracts. Cell 87:53–63

    PubMed  CAS  Google Scholar 

  30. Cook JG, Chasse DA, Nevins JR (2004) The regulated association of Cdt1 with minichromosome maintenance proteins and Cdc6 in mammalian cells. J Biol Chem 279:9625–9633

    PubMed  CAS  Google Scholar 

  31. Costanzo V, Shechter D, Lupardus PJ, Cimprich KA, Gottesman M, Gautier J (2003) An ATR- and Cdc7-dependent DNA damage checkpoint that inhibits initiation of DNA replication. Mol Cell 11:203–213

    PubMed  CAS  Google Scholar 

  32. Coverley D, Pelizon C, Trewick S, Laskey RA (2000) Chromatin-bound Cdc6 persists in S and G2 phases in human cells, while soluble Cdc6 is destroyed in a cyclin A-cdk2 dependent process. J Cell Sci 113:1929–1938

    PubMed  CAS  Google Scholar 

  33. Delmolino LM, Saha P, Dutta A (2001) Multiple mechanisms regulate subcellular localization of human CDC6. J Biol Chem 276:26947–26954

    PubMed  CAS  Google Scholar 

  34. Dhar SK, Dutta A (2000) Identification and characterization of the human ORC6 homolog. J Biol Chem 275:34983–34988

    PubMed  CAS  Google Scholar 

  35. Dhar SK, Delmolino L, Dutta A (2001a) Architecture of the human origin recognition complex. J Biol Chem 276:29067–29071

    PubMed  CAS  Google Scholar 

  36. Dhar SK, Yoshida K, Machida Y, Khaira P, Chaudhuri B, Wohlschlegel JA, Leffak M, Yates J, Dutta A (2001b) Replication from oriP of Epstein-Barr virus requires human ORC and is inhibited by geminin. Cell 106:287–296

    PubMed  CAS  Google Scholar 

  37. Dijkwel PA, Hamlin JL (1995) The Chinese hamster dihydrofolate reductase origin consists of multiple potential nascent-strand start sites. Mol Cell Biol 15:3023–3031

    PubMed  CAS  Google Scholar 

  38. Dijkwel PA, Wang S, Hamlin JL (2002) Initiation sites are distributed at frequent intervals in the Chinese hamster dihydrofolate reductase origin of replication but are used with very different efficiencies. Mol Cell Biol 22:3053–3065

    PubMed  CAS  Google Scholar 

  39. Dolan WP, Sherman DA, Forsburg SL (2004) Schizosaccharomyces pombe replication protein Cdc45/Sna41 requires Hsk1/Cdc7 and Rad4/Cut5 for chromatin binding. Chromosoma 113:145–156

    PubMed  CAS  Google Scholar 

  40. Donaldson AD, Fangman WL, Brewer BJ (1998). Cdc7 is required throughout the yeast S phase to activate replication origins. Genes Dev 12:491–501

    PubMed  CAS  Google Scholar 

  41. Donovan S, Harwood J, Drury LS, Diffley JF (1997) Cdc6p-dependent loading of Mcm proteins onto pre-replicative chromatin in budding yeast. Proc Natl Acad Sci USA 94:5611–5616

    PubMed  CAS  Google Scholar 

  42. Drury LS, Perkins G, Diffley JF (1997) The Cdc4/34/53 pathway targets Cdc6p for proteolysis in budding yeast. Embo J 16:5966–5976

    PubMed  CAS  Google Scholar 

  43. Dubey DD, Kim SM, Todorov IT, Huberman JA (1996) Large, complex modular structure of a fission yeast DNA replication origin. Curr Biol 6:467–473

    PubMed  CAS  Google Scholar 

  44. Dutta A, Bell SP (1997) Initiation of DNA replication in eukaryotic cells. Annu Rev Cell Dev Biol 13:293–332

    PubMed  CAS  Google Scholar 

  45. Elsasser S, Chi Y, Yang P, Campbell JL (1999) Phosphorylation controls timing of Cdc6p destruction: A biochemical analysis. Mol Biol Cell 10:3263–3277

    PubMed  CAS  Google Scholar 

  46. Ferreira MF, Santocanale C, Drury LS, Diffley JF (2000) Dbf4p, an essential S phase-promoting factor, is targeted for degradation by the anaphase-promoting complex. Mol Cell Biol 20:242–248

    PubMed  CAS  Google Scholar 

  47. Findeisen M, El-Denary M, Kapitza T, Graf R, Strausfeld U (1999) Cyclin A-dependent kinase activity affects chromatin binding of ORC, Cdc6, and MCM in egg extracts of Xenopus laevis. Eur J Biochem 264:415–426

    PubMed  CAS  Google Scholar 

  48. Fletcher RJ, Bishop BE, Leon RP, Sclafani RA, Ogata CM, Chen XS (2003) The structure and function of MCM from archaeal M. Thermoautotrophicum. Nat Struct Biol 10:160–167

    PubMed  CAS  Google Scholar 

  49. Fujita M, Ishimi Y, Nakamura H, Kiyono T, Tsurumi T (2002) Nuclear organization of DNA replication initiation proteins in mammalian cells. J Biol Chem 277:10354–10361

    PubMed  CAS  Google Scholar 

  50. Fujita M, Yamada C, Goto H, Yokoyama N, Kuzushima K, Inagaki M, Tsurumi T (1999) Cell cycle regulation of human CDC6 protein. Intracellular localization, interaction with the human mcm complex, and CDC2 kinase-mediated hyperphosphorylation. J Biol Chem 274:25927–25932

    PubMed  CAS  Google Scholar 

  51. Gavin KA, Hidaka M, Stillman B (1995) Conserved initiator proteins in eukaryotes. Science 270:1667–1671

    PubMed  CAS  Google Scholar 

  52. Gilbert DM, Miyazawa H, DePamphilis ML (1995) Site-specific initiation of DNA replication in Xenopus egg extract requires nuclear structure. Mol Cell Biol 15:2942–2954

    PubMed  CAS  Google Scholar 

  53. Gillespie PJ, Li A, Blow JJ (2001) Reconstitution of licensed replication origins on Xenopus sperm nuclei using purified proteins. BMC Biochem 2:15

    PubMed  CAS  Google Scholar 

  54. Goren A, Cedar H (2003) Replicating by the clock. Nat Rev Mol Cell Biol 4:25–32

    PubMed  CAS  Google Scholar 

  55. Gossen M, Pak DT, Hansen SK, Acharya JK, Botchan MR (1995) A Drosophila homolog of the yeast origin recognition complex. Science 270:1674–1677

    PubMed  CAS  Google Scholar 

  56. Gregan J, Lindner K, Brimage L, Franklin R, Namdar M, Hart EA, Aves SJ, Kearsey SE (2003) Fission yeast Cdc23/Mcm10 functions after pre-replicative complex formation to promote Cdc45 chromatin binding. Mol Biol Cell 14:3876–3887

    PubMed  CAS  Google Scholar 

  57. Hardy CF, Dryga O, Seematter S, Pahl PM, Sclafani RA (1997) mcm5/cdc46-bob1 bypasses the requirement for the S phase activator Cdc7p. Proc Natl Acad Sci USA 94:3151–3155

    PubMed  CAS  Google Scholar 

  58. Hartwell LH (1976) Sequential function of gene products relative to DNA synthesis in the yeast cell cycle. J Mol Biol 104:803–817

    PubMed  CAS  Google Scholar 

  59. Hartwell LH, Culotti J, Pringle JR, Reid BJ (1974) Genetic control of the cell division cycle in yeast. Science 183:46–51

    PubMed  CAS  Google Scholar 

  60. Harvey KJ, Newport J (2003) Metazoan origin selection: origin recognition complex chromatin binding is regulated by CDC6 recruitment and ATP hydrolysis. J Biol Chem 278:48524–48528

    PubMed  CAS  Google Scholar 

  61. Heintz NH, Hamlin JL (1982) An amplified chromosomal sequence that includes the gene for dihydrofolate reductase initiates replication within specific restriction fragments. Proc Natl Acad Sci USA 79:4083–4087

    PubMed  CAS  Google Scholar 

  62. Heintz NH, Milbrandt JD, Greisen KS, Hamlin JL (1983) Cloning of the initiation region of a mammalian chromosomal replicon. Nature 302:439–441

    PubMed  CAS  Google Scholar 

  63. Hennessy KM, Lee A, Chen E, Botstein D (1991) A group of interacting yeast DNA replication genes. Genes Dev 5:958–969

    PubMed  CAS  Google Scholar 

  64. Herbig U, Marlar CA, Fanning E (1999) The Cdc6 nucleotide-binding site regulates its activity in DNA replication in human cells. Mol Biol Cell 10:2631–2645

    PubMed  CAS  Google Scholar 

  65. Higa LA, Mihaylov IS, Banks DP, Zheng J, Zhang H (2003) Radiation-mediated proteolysis of CDT1 by CUL4-ROC1 and CSN complexes constitutes a new checkpoint. Nat Cell Biol 5:1008–1015

    PubMed  CAS  Google Scholar 

  66. Hofmann JF, Beach D (1994) cdt1 is an essential target of the Cdc10/Sct1 transcription factor: requirement for DNA replication and inhibition of mitosis. Embo J 13:425–434

    PubMed  CAS  Google Scholar 

  67. Homesley L, Lei M, Kawasaki Y, Sawyer S, Christensen T, Tye BK (2000) Mcm10 and the MCM2-7 complex interact to initiate DNA synthesis and to release replication factors from origins. Genes Dev 14:913–926

    PubMed  CAS  Google Scholar 

  68. Hopwood B, Dalton S (1996) Cdc45p assembles into a complex with Cdc46p/Mcm5p, is required for minichromosome maintenance, and is essential for chromosomal DNA replication. Proc Natl Acad Sci USA 93:12309–12314

    PubMed  CAS  Google Scholar 

  69. Hu J, McCall CM, Ohta T, Xiong Y (2004) Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response to DNA damage. Nat Cell Biol 6:1003–1009

    PubMed  CAS  Google Scholar 

  70. Hua XH, Newport J (1998) Identification of a preinitiation step in DNA replication that is independent of origin recognition complex and cdc6, but dependent on cdk2. J Cell Biol 140:271–281

    PubMed  CAS  Google Scholar 

  71. Hyrien O, Mechali M (1992) Plasmid replication in Xenopus eggs and egg extracts: a 2D gel electrophoretic analysis. Nucleic Acids Res 20:1463–1469

    PubMed  CAS  Google Scholar 

  72. Hyrien O, Mechali M (1993) Chromosomal replication initiates and terminates at random sequences but at regular intervals in the ribosomal DNA of Xenopus early embryos. Embo J 12:4511–4520

    PubMed  CAS  Google Scholar 

  73. Hyrien O, Maric C, Mechali M (1995) Transition in specification of embryonic metazoan DNA replication origins. Science 270:994–997

    PubMed  CAS  Google Scholar 

  74. Ishimi Y (1997) A DNA helicase activity is associated with an MCM4, -6, and -7 protein complex. J Biol Chem 272:24508–24513

    PubMed  CAS  Google Scholar 

  75. Izumi M, Yatagai F, Hanaoka F (2001) Cell cycle-dependent proteolysis and phosphorylation of human Mcm10. J Biol Chem 276:48526–48531

    PubMed  CAS  Google Scholar 

  76. Jacob F, Brenner S, Cuzin F (1963) On the regulation of DNA replication in bacteria. Cold Spring Harbor Symp Quant Biol 28:329–348

    CAS  Google Scholar 

  77. Jallepalli PV, Brown GW, Muzi-Falconi M, Tien D, Kelly TJ (1997) Regulation of the replication initiator protein p65cdc18 by CDK phosphorylation. Genes Dev 11:2767–2779

    PubMed  CAS  Google Scholar 

  78. Jeon Y, Bekiranov S, Karnani N, Kapranov P, Ghosh S, Macalpine DM, Lee C, Hwang DS, Gingeras TR, Dutta A (2005) Temporal profile of replication of human chromosomes. Proc Natl Acad Sci USA 102:6419–6424

    PubMed  CAS  Google Scholar 

  79. Jiang W, Wells NJ, Hunter T (1999) Multistep regulation of DNA replication by Cdk phosphorylation of HsCdc6. Proc Natl Acad Sci USA 96:6193–6198

    PubMed  CAS  Google Scholar 

  80. Kalejta RF, Li X, Mesner LD, Dijkwel PA, Lin HB, Hamlin JL (1998) Distal sequences, but not ori-beta/OBR-1, are essential for initiation of DNA replication in the Chinese hamster DHFR origin. Mol Cell 2:797–806

    PubMed  CAS  Google Scholar 

  81. Kamimura Y, Masumoto H, Sugino A, Araki H (1998) Sld2, which interacts with Dpb11 in Saccharomyces cerevisiae, is required for chromosomal DNA replication. Mol Cell Biol 18:6102–6109

    PubMed  CAS  Google Scholar 

  82. Kamimura Y, Tak YS, Sugino A, Araki H (2001) Sld3, which interacts with Cdc45 (Sld4), functions for chromosomal DNA replication in Saccharomyces cerevisiae. Embo J 20:2097–2107

    PubMed  CAS  Google Scholar 

  83. Kanemaki M, Sanchez-Diaz A, Gambus A, Labib K (2003) Functional proteomic identification of DNA replication proteins by induced proteolysis in vivo. Nature 423:720–724

    PubMed  CAS  Google Scholar 

  84. Karakaidos P, Taraviras S, Vassiliou LV, Zacharatos P, Kastrinakis NG, Kougiou D, Kouloukoussa M, Nishitani H, Papavassiliou AG, Lygerou Z, Gorgoulis VG (2004) Overexpression of the replication licensing regulators hCdt1 and hCdc6 characterizes a subset of non-small-cell lung carcinomas: synergistic effect with mutant p53 on tumor growth and chromosomal instability–evidence of E2F-1 transcriptional control over hCdt1. Am J Pathol 165:1351–1365

    PubMed�� CAS  Google Scholar 

  85. Kearsey SE, Montgomery S, Labib K, Lindner K (2000) Chromatin binding of the fission yeast replication factor mcm4 occurs during anaphase and requires ORC and cdc18. Embo J 19:1681–1690

    PubMed  CAS  Google Scholar 

  86. Kelly TJ, Brown GW (2000) Regulation of chromosome replication. Annu Rev Biochem 69:829–880

    PubMed  CAS  Google Scholar 

  87. Kelman Z, Lee JK, Hurwitz J (1999) The single minichromosome maintenance protein of Methanobacterium thermoautotrophicum DeltaH contains DNA helicase activity. Proc Natl Acad Sci USA 96:14783–14788

    PubMed  CAS  Google Scholar 

  88. Kihara M, Nakai W, Asano S, Suzuki A, Kitada K, Kawasaki Y, Johnston LH, Sugino A (2000) Characterization of the yeast Cdc7p/Dbf4p complex purified from insect cells. Its protein kinase activity is regulated by Rad53p. J Biol Chem 275:35051–35062

    PubMed  CAS  Google Scholar 

  89. Kitsberg D, Selig S, Keshet I, Cedar H (1993) Replication structure of the human beta-globin gene domain. Nature 366:588–590

    PubMed  CAS  Google Scholar 

  90. Kobayashi T, Rein T, DePamphilis ML (1998) Identification of primary initiation sites for DNA replication in the hamster dihydrofolate reductase gene initiation zone. Mol Cell Biol 18:3266–3277

    PubMed  CAS  Google Scholar 

  91. Kondo T, Kobayashi M, Tanaka J, Yokoyama A, Suzuki S, Kato N, Onozawa M, Chiba K, Hashino S, Imamura M et al. (2004) Rapid degradation of Cdt1 upon UV-induced DNA damage is mediated by SCFSkp2 complex. J Biol Chem 279:27315–27319

    PubMed  CAS  Google Scholar 

  92. Kong D, DePamphilis ML (2001) Site-specific DNA binding of the Schizosaccharomyces pombe origin recognition complex is determined by the Orc4 subunit. Mol Cell Biol 21:8095–8103

    PubMed  CAS  Google Scholar 

  93. Koonin EV (1993). A common set of conserved motifs in a vast variety of putative nucleic acid-dependent ATPases including MCM proteins involved in the initiation of eukaryotic DNA replication. Nucleic Acids Res 21:2541–2547

    PubMed  CAS  Google Scholar 

  94. Kubota Y, Mimura S, Nishimoto S, Masuda T, Nojima H, Takisawa H (1997) Licensing of DNA replication by a multi-protein complex of MCM/P1 proteins in Xenopus eggs. Embo J 16:3320–3331

    PubMed  CAS  Google Scholar 

  95. Kubota Y, Takase Y, Komori Y, Hashimoto Y, Arata T, Kamimura Y, Araki H, Takisawa H (2003) A novel ring-like complex of Xenopus proteins essential for the initiation of DNA replication. Genes Dev 17:1141–1152

    PubMed  CAS  Google Scholar 

  96. Kumagai H, Sato N, Yamada M, Mahony D, Seghezzi W, Lees E, Arai K, Masai H (1999) A novel growth- and cell cycle-regulated protein, ASK, activates human Cdc7-related kinase and is essential for G1/S transition in mammalian cells. Mol Cell Biol 19:5083–5095

    PubMed  CAS  Google Scholar 

  97. Labib K, Diffley JF, Kearsey SE (1999) G1-phase and B-type cyclins exclude the DNA-replication factor Mcm4 from the nucleus. Nat Cell Biol 1:415–422

    PubMed  CAS  Google Scholar 

  98. Labib K, Tercero JA, Diffley JF (2000) Uninterrupted MCM2-7 function required for DNA replication fork progression. Science 288:1643–1647

    PubMed  CAS  Google Scholar 

  99. Leatherwood J, Lopez-Girona A, Russell P (1996) Interaction of Cdc2 and Cdc18 with a fission yeast ORC2-like protein. Nature 379:360–363

    PubMed  CAS  Google Scholar 

  100. Lee C, Hong B, Choi JM, Kim Y, Watanabe S, Ishimi Y, Enomoto T, Tada S, Cho Y (2004) Structural basis for inhibition of the replication licensing factor Cdt1 by geminin. Nature 430:913–917

    PubMed  CAS  Google Scholar 

  101. Lee JK, Hurwitz J (2000) Isolation and characterization of various complexes of the minichromosome maintenance proteins of Schizosaccharomyces pombe. J Biol Chem 275:18871–18878

    PubMed  CAS  Google Scholar 

  102. Lee JK, Seo YS, Hurwitz J (2003) The Cdc23 (Mcm10) protein is required for the phosphorylation of minichromosome maintenance complex by the Dfp1-Hsk1 kinase. Proc Natl Acad Sci USA 100:2334–2339

    PubMed  CAS  Google Scholar 

  103. Lee JK, Moon KY, Jiang Y, Hurwitz J (2001) The Schizosaccharomyces pombe origin recognition complex interacts with multiple AT-rich regions of the replication origin DNA by means of the AT-hook domains of the spOrc4 protein. Proc Natl Acad Sci USA 98:13589–13594

    PubMed  CAS  Google Scholar 

  104. Lei M, Kawasaki Y, Young MR, Kihara M, Sugino A, Tye BK (1997) Mcm2 is a target of regulation by Cdc7-Dbf4 during the initiation of DNA synthesis. Genes Dev 11:3365–3374

    PubMed  CAS  Google Scholar 

  105. Li A, Blow JJ (2004) Cdt1 downregulation by proteolysis and geminin inhibition prevents DNA re-replication in Xenopus. Embo J 24:395–404

    PubMed  Google Scholar 

  106. Li CJ, DePamphilis ML (2002) Mammalian Orc1 protein is selectively released from chromatin and ubiquitinated during the S-to-M transition in the cell division cycle. Mol Cell Biol 22:105–116

    PubMed  Google Scholar 

  107. 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 24:5875–5886

    PubMed  CAS  Google Scholar 

  108. Li D, Zhao R, Lilyestrom W, Gai D, Zhang R, DeCaprio JA, Fanning E, Jochimiak A, Szakonyi G, Chen XS (2003a) Structure of the replicative helicase of the oncoprotein SV40 large tumour antigen. Nature 423:512–518

    PubMed  CAS  Google Scholar 

  109. Li X, Zhao Q, Liao R, Sun P, Wu X (2003b) The SCFSkp2 ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation. J Biol Chem 278:30854–30858

    PubMed  CAS  Google Scholar 

  110. Liang C, Weinreich M, Stillman B (1995) ORC and Cdc6p interact and determine the frequency of initiation of DNA replication in the genome. Cell 81:667–676

    PubMed  CAS  Google Scholar 

  111. Liu G, Malott M, Leffak M (2003) Multiple functional elements comprise a mammalian chromosomal replicator. Mol Cell Biol 23:1832–1842

    PubMed  CAS  Google Scholar 

  112. Liu J, Smith CL, DeRyckere D, DeAngelis K, Martin GS, Berger JM (2000) Structure and function of Cdc6/Cdc18: implications for origin recognition and checkpoint control. Mol Cell 6:637–648

    PubMed  CAS  Google Scholar 

  113. Macalpine DM, Rodriguez HK, Bell SP (2004) Coordination of replication and transcription along a Drosophila chromosome. Genes Dev 18:3094–3105

    PubMed  CAS  Google Scholar 

  114. Madine MA, Khoo CY, Mills AD, Laskey RA (1995) MCM3 complex required for cell cycle regulation of DNA replication in vertebrate cells. Nature 375:421–424

    PubMed  CAS  Google Scholar 

  115. Mahbubani HM, Paull T, Elder JK, Blow JJ (1992) DNA replication initiates at multiple sites on plasmid DNA in Xenopus egg extracts. Nucleic Acids Res 20:1457–1462

    PubMed  CAS  Google Scholar 

  116. Maine GT, Sinha P, Tye BK (1984) Mutants of S. cerevisiae defective in the maintenance of minichromosomes. Genetics 106:365–385

    PubMed  CAS  Google Scholar 

  117. Maiorano D, Moreau J, Mechali M (2000) XCDT1 is required for the assembly of pre-replicative complexes in Xenopus laevis. Nature 404:622–625

    PubMed  CAS  Google Scholar 

  118. Marahrens Y, Stillman B (1992) A yeast chromosomal origin of DNA replication defined by multiple functional elements. Science 255:817–823

    PubMed  CAS  Google Scholar 

  119. Masai H, Arai K (2002) Cdc7 kinase complex: a key regulator in the initiation of DNA replication. J Cell Physiol 190:287–296

    PubMed  CAS  Google Scholar 

  120. Masuda HP, Ramos GB, de Almeida-Engler J, Cabral LM, Coqueiro VM, Macrini CM, Ferreira PC, Hemerly AS (2004) Genome based identification and analysis of the pre-replicative complex of Arabidopsis thaliana. FEBS Lett 574:192–202

    PubMed  CAS  Google Scholar 

  121. Masuda T, Mimura S, Takisawa H (2003) CDK- and Cdc45-dependent priming of the MCM complex on chromatin during S-phase in Xenopusenopus egg extracts: possible activation of MCM helicase by association with Cdc45. Genes Cells 8:145–161

    PubMed  CAS  Google Scholar 

  122. Masumoto H, Sugino A, Araki H (2000) Dpb11 controls the association between DNA polymerases alpha and epsilon and the autonomously replicating sequence region of budding yeast. Mol Cell Biol 20:2809–2817

    PubMed  CAS  Google Scholar 

  123. Masumoto H, Muramatsu S, Kamimura Y, Araki H (2002) S-Cdk-dependent phosphorylation of Sld2 essential for chromosomal DNA replication in budding yeast. Nature 415:651–655

    PubMed  CAS  Google Scholar 

  124. McGarry TJ, Kirschner MW (1998) Geminin, an inhibitor of DNA replication, is degraded during mitosis. Cell 93:1043–1053

    PubMed  CAS  Google Scholar 

  125. Melixetian M, Ballabeni A, Masiero L, Gasparini P, Zamponi R, Bartek J, Lukas J, Helin K (2004) Loss of Geminin induces rereplication in the presence of functional p53. J Cell Biol 165:473–482

    PubMed  CAS  Google Scholar 

  126. Mendez J, Stillman B (2000) Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis. Mol Cell Biol 20:8602–8612

    PubMed  CAS  Google Scholar 

  127. Mendez J, Zou-Yang XH, Kim SY, Hidaka M, Tansey WP, Stillman B (2002) Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication. Mol Cell 9:481–491

    PubMed  CAS  Google Scholar 

  128. Merchant AM, Kawasaki Y, Chen Y, Lei M, Tye BK (1997) A lesion in the DNA replication initiation factor Mcm10 induces pausing of elongation forks through chromosomal replication origins in Saccharomyces cerevisiae. Mol Cell Biol 17:3261–3271

    PubMed  CAS  Google Scholar 

  129. Mesner LD, Li X, Dijkwel PA, Hamlin JL (2003) The dihydrofolate reductase origin of replication does not contain any nonredundant genetic elements required for origin activity. Mol Cell Biol 23:804–814

    PubMed  CAS  Google Scholar 

  130. Mimura S, Takisawa H (1998) Xenopus Cdc45-dependent loading of DNA polymerase alpha onto chromatin under the control of S-phase Cdk. Embo J 17:5699–5707

    PubMed  CAS  Google Scholar 

  131. Mizushima T, Takahashi N, Stillman B (2000) Cdc6p modulates the structure and DNA binding activity of the origin recognition complex in vitro. Genes Dev 14:1631–1641

    CAS  Google Scholar 

  132. Moir D, Stewart SE, Osmond BC, Botstein D (1982) Cold-sensitive cell-division-cycle mutants of yeast: isolation, properties, and pseudoreversion studies. Genetics 100:547–563

    PubMed  CAS  Google Scholar 

  133. Moon KY, Kong D, Lee JK, Raychaudhuri S, Hurwitz J (1999) Identification and reconstitution of the origin recognition complex from Schizosaccharomyces pombe. Proc Natl Acad Sci USA 96:12367–12372

    PubMed  CAS  Google Scholar 

  134. Muller M, Lucchini R, Sogo JM (2000) Replication of yeast rDNA initiates downstream of transcriptionally active genes. Mol Cell 5:767–777

    PubMed  CAS  Google Scholar 

  135. Muzi-Falconi M, Brown GW, Kelly TJ (1996) cdc18+ regulates initiation of DNA replication in Schizosaccharomyces pombe. Proc Natl Acad Sci USA 93:1566–1570

    PubMed  CAS  Google Scholar 

  136. Muzi-Falconi M, Kelly TJ (1995) Orp1, a member of the Cdc18/Cdc6 family of S-phase regulators, is homologous to a component of the origin recognition complex. Proc Natl Acad Sci USA 92:12475–12479

    PubMed  CAS  Google Scholar 

  137. Nakajima R, Masukata H (2002) SpSld3 is required for loading and maintenance of SpCdc45 on chromatin in DNA replication in fission yeast. Mol Biol Cell 13:1462–1472

    PubMed  CAS  Google Scholar 

  138. Neuwald AF, Aravind L, Spouge JL, Koonin EV (1999) AAA+: A class of chaperone-like ATPases associated with the assembly, operation, and disassembly of protein complexes. Genome Res 9:27–43

    PubMed  CAS  Google Scholar 

  139. Nguyen VQ, Co C, Li JJ (2001) Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms. Nature 411:1068–1073

    PubMed  CAS  Google Scholar 

  140. Nguyen VQ, Co C, Irie K, Li JJ (2000) Clb/Cdc28 kinases promote nuclear export of the replication initiator proteins Mcm2-7. Curr Biol 10:195–205

    PubMed  CAS  Google Scholar 

  141. Nishitani H, Nurse P (1995) p65cdc18 plays a major role controlling the initiation of DNA replication in fission yeast. Cell 83:397–405

    PubMed  CAS  Google Scholar 

  142. Nishitani H, Lygerou Z, Nishimoto T, Nurse P (2000) The Cdt1 protein is required to license DNA for replication in fission yeast. Nature 404:625–628

    PubMed  CAS  Google Scholar 

  143. Nishitani H, Taraviras S, Lygerou Z, Nishimoto T (2001) The human licensing factor for DNA replication Cdt1 accumulates in G1 and is destabilized after initiation of S-phase. J Biol Chem 276:44905–44911

    PubMed  CAS  Google Scholar 

  144. Ohtani K, Tsujimoto A, Ikeda M, Nakamura M (1998) Regulation of cell growth-dependent expression of mammalian CDC6 gene by the cell cycle transcription factor E2F. Oncogene 17:1777–1785

    PubMed  CAS  Google Scholar 

  145. Oshiro G, Owens JC, Shellman Y, Sclafani RA, Li JJ (1999) Cell cycle control of Cdc7p kinase activity through regulation of Dbf4p stability. Mol Cell Biol 19:4888–4896

    PubMed  CAS  Google Scholar 

  146. Owens JC, Detweiler CS, Li JJ (1997) CDC45 is required in conjunction with CDC7/DBF4 to trigger the initiation of DNA replication. Proc Natl Acad Sci USA 94:12521–12526

    PubMed  CAS  Google Scholar 

  147. Pacek M, Walter JC (2004) A requirement for MCM7 and Cdc45 in chromosome unwinding during eukaryotic DNA replication. Embo J 23:3667–3676

    PubMed  CAS  Google Scholar 

  148. Paixao S, Colaluca IN, Cubells M, Peverali FA, Destro A, Giadrossi S, Giacca M, Falaschi A, Riva S, Biamonti G (2004) Modular structure of the human lamin B2 replicator. Mol Cell Biol 24:2958–2967

    PubMed  CAS  Google Scholar 

  149. Parrilla-Castellar ER, Karnitz LM (2003) Cut5 is required for the binding of Atr and DNA polymerase alpha to genotoxin-damaged chromatin. J Biol Chem 278:45507–45511

    PubMed  CAS  Google Scholar 

  150. Pelizon C, d'Adda di Fagagna F, Farrace L, Laskey RA (2002) Human replication protein Cdc6 is selectively cleaved by caspase 3 during apoptosis. EMBO Rep 3:780–784

    PubMed  CAS  Google Scholar 

  151. Perkins G, Diffley JF (1998) Nucleotide-dependent prereplicative complex assembly by Cdc6p, a homolog of eukaryotic and prokaryotic clamp-loaders. Mol Cell 2:23–32

    PubMed  CAS  Google Scholar 

  152. Petersen BO, Lukas J, Sorensen CS, Bartek J, Helin K (1999) Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization. Embo J 18:396–410

    PubMed  CAS  Google Scholar 

  153. Pinto S, Quintana DG, Smith P, Mihalek RM, Hou ZH, Boynton S, Jones CJ, Hendricks M, Velinzon K, Wohlschlegel JA et al. (1999) latheo encodes a subunit of the origin recognition complex and disrupts neuronal proliferation and adult olfactory memory when mutant. Neuron 23:45–54

    PubMed  CAS  Google Scholar 

  154. Quintana DG, Hou Z, Thome KC, Hendricks M, Saha P, Dutta A (1997) Identification of HsORC4, a member of the human origin of replication recognition complex. J Biol Chem 272:28247–28251

    PubMed  CAS  Google Scholar 

  155. Quintana DG, Thome KC, Hou ZH, Ligon AH, Morton CC, Dutta A (1998) ORC5L, a new member of the human origin recognition complex, is deleted in uterine leiomyomas and malignant myeloid diseases. J Biol Chem 273:27137–27145

    PubMed  CAS  Google Scholar 

  156. Raghuraman MK, Winzeler EA, Collingwood D, Hunt S, Wodicka L, Conway A, Lockhart DJ, Davis RW, Brewer BJ, Fangman WL (2001) Replication dynamics of the yeast genome. Science 294:115–121

    PubMed  CAS  Google Scholar 

  157. Reid RJ, Fiorani P, Sugawara M, Bjornsti MA (1999) CDC45 and DPB11 are required for processive DNA replication and resistance to DNA topoisomerase I-mediated DNA damage. Proc Natl Acad Sci USA 96:11440–11445

    PubMed  CAS  Google Scholar 

  158. Remus D, Beall EL, Botchan MR (2004) DNA topology, not DNA sequence, is a critical determinant for Drosophila ORC-DNA binding. Embo J 23:897–907

    PubMed  CAS  Google Scholar 

  159. Ricke RM, Bielinsky AK (2004) Mcm10 regulates the stability and chromatin association of DNA polymerase-alpha. Mol Cell 16:173–185

    PubMed  CAS  Google Scholar 

  160. Ritzi M, Tillack K, Gerhardt J, Ott E, Humme S, Kremmer E, Hammerschmidt W, Schepers A (2003) Complex protein-DNA dynamics at the latent origin of DNA replication of Epstein-Barr virus. J Cell Sci 116:3971–3984

    PubMed  CAS  Google Scholar 

  161. Rowles A, Tada S, Blow JJ (1999) Changes in association of the Xenopus origin recognition complex with chromatin on licensing of replication origins. J Cell Sci 112:2011–2018

    PubMed  CAS  Google Scholar 

  162. Rowley A, Cocker JH, Harwood J, Diffley JF (1995) Initiation complex assembly at budding yeast replication origins begins with the recognition of a bipartite sequence by limiting amounts of the initiator, ORC. Embo J 14:2631–2641

    PubMed  CAS  Google Scholar 

  163. Saha P, Chen J, Thome KC, Lawlis SJ, Hou ZH, Hendricks M, Parvin JD, Dutta A (1998) Human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively eliminated from the nucleus at the onset of S phase. Mol Cell Biol 18:2758–2767

    PubMed  CAS  Google Scholar 

  164. Saha S, Shan Y, Mesner LD, Hamlin JL (2004) The promoter of the Chinese hamster ovary dihydrofolate reductase gene regulates the activity of the local origin and helps define its boundaries. Genes Dev 18:397–410

    PubMed  CAS  Google Scholar 

  165. Saka Y, Yanagida M (1993) Fission yeast cut5+, required for S phase onset and M phase restraint, is identical to the radiation-damage repair gene rad4+. Cell 74:383–393

    PubMed  CAS  Google Scholar 

  166. Sasaki T, Sawado T, Yamaguchi M, Shinomiya T (1999) Specification of regions of DNA replication initiation during embryogenesis in the 65-kilobase DNApolalpha-dE2F locus of Drosophila melanogaster. Mol Cell Biol 19:547–555

    PubMed  CAS  Google Scholar 

  167. Sato M, Gotow T, You Z, Komamura-Kohno Y, Uchiyama Y, Yabuta N, Nojima H, Ishimi Y (2000) Electron microscopic observation and single-stranded DNA binding activity of the Mcm4,6,7 complex. J Mol Biol 300:421–431

    PubMed  CAS  Google Scholar 

  168. Sato N, Arai K, Masai H (1997) Human and Xenopus cDNAs encoding budding yeast Cdc7-related kinases: in vitro phosphorylation of MCM subunits by a putative human homologue of Cdc7. Embo J 16:4340–4351

    PubMed  CAS  Google Scholar 

  169. Saxena S, Yuan P, Dhar SK, Senga T, Takeda D, Robinson H, Kornbluth S, Swaminathan K, Dutta A (2004) A dimerized coiled-coil domain and an adjoining part of geminin interact with two sites on Cdt1 for replication inhibition. Mol Cell 15:245–258

    PubMed  CAS  Google Scholar 

  170. Schepers A, Diffley JF (2001) Mutational analysis of conserved sequence motifs in the budding yeast Cdc6 protein. J Mol Biol 308:597–608

    PubMed  CAS  Google Scholar 

  171. Schepers A, Ritzi M, Bousset K, Kremmer E, Yates JL, Harwood J, Diffley JF, Hammerschmidt W (2001) Human origin recognition complex binds to the region of the latent origin of DNA replication of Epstein-Barr virus. Embo J 20:4588–4602

    PubMed  CAS  Google Scholar 

  172. Schubeler D, Scalzo D, Kooperberg C, van Steensel B, Delrow J, Groudine M (2002) Genome-wide DNA replication profile for Drosophila melanogaster: a link between transcription and replication timing. Nat Genet 32:438–442

    PubMed  Google Scholar 

  173. Schwacha A, Bell SP (2001) Interactions between two catalytically distinct MCM subgroups are essential for coordinated ATP hydrolysis and DNA replication. Mol Cell 8:1093–1104

    PubMed  CAS  Google Scholar 

  174. Seki T, Diffley JF (2000) Stepwise assembly of initiation proteins at budding yeast replication origins in vitro. Proc Natl Acad Sci USA 97:14115–14120

    PubMed  CAS  Google Scholar 

  175. Semple JW, Duncker BP (2004) ORC-associated replication factors as biomarkers for cancer. Biotechnol Adv 22:621–631

    PubMed  CAS  Google Scholar 

  176. Shechter DF, Ying CY, Gautier J (2000) The intrinsic DNA helicase activity of Methanobacterium thermoautotrophicum delta H minichromosome maintenance protein. J Biol Chem 275:15049–15059

    PubMed  CAS  Google Scholar 

  177. Solomon NA, Wright MB, Chang S, Buckley AM, Dumas LB, Gaber RF (1992) Genetic and molecular analysis of DNA43 and DNA52: two new cell-cycle genes in Saccharomyces cerevisiae. Yeast 8:273–289

    PubMed  CAS  Google Scholar 

  178. Stedman W, Deng Z, Lu F, Lieberman PM (2004) ORC, MCM, and histone hyperacetylation at the Kaposi's sarcoma-associated herpesvirus latent replication origin. J Virol 78:12566–12575

    PubMed  CAS  Google Scholar 

  179. Stinchcomb DT, Struhl K, Davis RW (1979) Isolation and characterisation of a yeast chromosomal replicator. Nature 282:39–43

    PubMed  CAS  Google Scholar 

  180. Stoeber K, Mills AD, Kubota Y, Krude T, Romanowski P, Marheineke K, Laskey RA, Williams GH (1998) Cdc6 protein causes premature entry into S phase in a mammalian cell-free system. Embo J 17:7219–7229

    PubMed  CAS  Google Scholar 

  181. Struhl K, Stinchcomb DT, Scherer S, Davis RW (1979) High-frequency transformation of yeast: autonomous replication of hybrid DNA molecules. Proc Natl Acad Sci USA 76:1035–1039

    PubMed  CAS  Google Scholar 

  182. Sugimoto N, Tatsumi Y, Tsurumi T, Matsukage A, Kiyono T, Nishitani H, Fujita M (2004) Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding. J Biol Chem 279:19691–19697

    PubMed  CAS  Google Scholar 

  183. Tada S, Li A, Maiorano D, Mechali M, Blow JJ (2001) Repression of origin assembly in metaphase depends on inhibition of RLF-B/Cdt1 by geminin. Nat Cell Biol 3:107–113

    PubMed  CAS  Google Scholar 

  184. Takayama Y, Kamimura Y, Okawa M, Muramatsu S, Sugino A, Araki H (2003) GINS, a novel multiprotein complex required for chromosomal DNA replication in budding yeast. Genes Dev 17:1153–1165

    PubMed  CAS  Google Scholar 

  185. Takeda DY, Parvin JD, Dutta A (2005) Degradation of Cdt1 during S-phase is SKP2 independent and is required for efficient progression of mammlian cells through S-phase. J Biol Chem (in press)

    Google Scholar 

  186. Takeda T, Ogino K, Matsui E, Cho MK, Kumagai H, Miyake T, Arai K, Masai H (1999) A fission yeast gene, him1(+)/dfp1(+) encoding a regulatory subunit for Hsk1 kinase, plays essential roles in S-phase initiation as well as in S-phase checkpoint control and recovery from DNA damage. Mol Cell Biol 19:5535–5547

    PubMed  CAS  Google Scholar 

  187. Tanaka S, Diffley JF (2002) Interdependent nuclear accumulation of budding yeast Cdt1 and Mcm2-7 during G1 phase. Nat Cell Biol 4:198–207

    PubMed  CAS  Google Scholar 

  188. Tanaka T, Knapp D, Nasmyth K (1997) Loading of an Mcm protein onto DNA replication origins is regulated by Cdc6p and CDKs. Cell 90:649–660

    PubMed  CAS  Google Scholar 

  189. Tatsumi Y, Ohta S, Kimura H, Tsurimoto T, Obuse C (2003) The ORC1 cycle in human cells: I. cell cycle-regulated oscillation of human ORC1. J Biol Chem 278:41528–41534

    PubMed  CAS  Google Scholar 

  190. Thommes P, Kubota Y, Takisawa H, Blow JJ (1997) The RLF-M component of the replication licensing system forms complexes containing all six MCM/P1 polypeptides. Embo J 16:3312–3319

    PubMed  CAS  Google Scholar 

  191. Tugal T, Zou-Yang XH, Gavin K, Pappin D, Canas B, Kobayashi R, Hunt T, Stillman B (1998) The Orc4p and Orc5p subunits of the Xenopus and human origin recognition complex are related to Orc1p and Cdc6p. J Biol Chem 273:32421–32429

    PubMed  CAS  Google Scholar 

  192. Van Hatten RA, Tutter AV, Holway AH, Khederian AM, Walter JC, Michael WM (2002) The Xenopus Xmus101 protein is required for the recruitment of Cdc45 to origins of DNA replication. J Cell Biol 159:541–547

    PubMed  Google Scholar 

  193. Vashee S, Simancek P, Challberg MD, Kelly TJ (2001) Assembly of the human origin recognition complex. J Biol Chem 276:26666–26673

    PubMed  CAS  Google Scholar 

  194. Vashee S, Cvetic C, Lu W, Simancek P, Kelly TJ, Walter JC (2003) Sequence-independent DNA binding replication initiation by the human origin recognition complex. Genes Dev 17:1894–1908

    CAS  Google Scholar 

  195. Vaughn JP, Dijkwel PA, Hamlin JL (1990) Replication initiates in a broad zone in the amplified CHO dihydrofolate reductase domain. Cell 61:1075–1087

    PubMed  CAS  Google Scholar 

  196. Vaziri C, Saxena S, Jeon Y, Lee C, Murata K, Machida Y, Wagle N, Hwang DS, Dutta A (2003) A p53-dependent checkpoint pathway prevents rereplication. Mol Cell 11:997–1008

    PubMed  CAS  Google Scholar 

  197. Walter J, Newport J (2000) Initiation of eukaryotic DNA replication: origin unwinding and sequential chromatin association of Cdc45, RPA, and DNA polymerase alpha. Mol Cell 5:617–627

    PubMed  CAS  Google Scholar 

  198. Wang H, Elledge SJ (1999) DRC1, DNA replication and checkpoint protein 1, functions with DPB11 to control DNA replication and the S-phase checkpoint in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 96:3824–3829

    PubMed  CAS  Google Scholar 

  199. Wang L, Lin CM, Brooks S, Cimbora D, Groudine M, Aladjem MI (2004) The human beta-globin replication initiation region consists of two modular independent replicators. Mol Cell Biol 24:3373–3386

    PubMed  CAS  Google Scholar 

  200. Weinreich M, Stillman B (1999) Cdc7p-Dbf4p kinase binds to chromatin during S phase and is regulated by both the APC and the RAD53 checkpoint pathway. Embo J 18:5334–5346

    PubMed  CAS  Google Scholar 

  201. Weinreich, M, Liang C, Stillman B (1999) The Cdc6p nucleotide-binding motif is required for loading mcm proteins onto chromatin. Proc Natl Acad Sci USA 96:441–446

    PubMed  CAS  Google Scholar 

  202. Williams GH, Romanowski P, Morris L, Madine M, Mills AD, Stoeber K, Marr J, Laskey RA, Coleman N (1998) Improved cervical smear assessment using antibodies against proteins that regulate DNA replication. Proc Natl Acad Sci USA 95:14932–14937

    PubMed  CAS  Google Scholar 

  203. Williams RS, Shohet RV, Stillman B (1997) A human protein related to yeast Cdc6p. Proc Natl Acad Sci USA 94:142–147

    PubMed  CAS  Google Scholar 

  204. Wilmes GM, Archambault V, Austin RJ, Jacobson MD, Bell SP, Cross FR (2004) Interaction of the S-phase cyclin Clb5 with an “RXL” docking sequence in the initiator protein Orc6 provides an origin-localized replication control switch. Genes Dev 18:981–991

    PubMed  CAS  Google Scholar 

  205. Wohlschlegel JA, Kutok JL, Weng AP, Dutta A (2002a) Expression of geminin as a marker of cell proliferation in normal tissues and malignancies. Am J Pathol 161:267–273

    PubMed  CAS  Google Scholar 

  206. Wohlschlegel JA, Dhar SK, Prokhorova TA, Dutta A, Walter JC (2002b) Xenopus Mcm10 binds to origins of DNA replication after Mcm2-7 and stimulates origin binding of Cdc45. Mol Cell 9:233–240

    PubMed  CAS  Google Scholar 

  207. Wohlschlegel JA, Dwyer BT, Dhar SK, Cvetic C, Walter JC, Dutta A (2000) Inhibition of eukaryotic DNA replication by geminin binding to Cdt1. Science 290:2309–2312

    PubMed  CAS  Google Scholar 

  208. Woodfine K, Fiegler H, Beare DM, Collins JE, McCann OT, Young BD, Debernardi S, Mott R, Dunham I, Carter NP (2004) Replication timing of the human genome. Hum Mol Genet 13:191–202

    PubMed  CAS  Google Scholar 

  209. Wu JR, Gilbert DM (1996) A distinct G1 step required to specify the Chinese hamster DHFR replication origin. Science 271:1270–1272

    PubMed  CAS  Google Scholar 

  210. Wuarin J, Buck V, Nurse P, Millar JB (2002) Stable association of mitotic cyclin B/Cdc2 to replication origins prevents endoreduplication. Cell 111:419–431

    PubMed  CAS  Google Scholar 

  211. Yamada Y, Nakagawa T, Masukata H (2004) A novel intermediate in initiation complex assembly for fission yeast DNA replication. Mol Biol Cell 15:3740–3750

    PubMed  CAS  Google Scholar 

  212. Yamane K, Wu X, Chen J (2002) A DNA damage-regulated BRCT-containing protein, TopBP1, is required for cell survival. Mol Cell Biol 22:555–566

    PubMed  CAS  Google Scholar 

  213. Yamane K, Chen J, Kinsella TJ (2003) Both DNA topoisomerase II-binding protein 1 and BRCA1 regulate the G2-M cell cycle checkpoint. Cancer Res 63:3049–3053

    PubMed  CAS  Google Scholar 

  214. Yan Z, DeGregori J, Shohet R, Leone G, Stillman B, Nevins JR, Williams RS (1998) Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells. Proc Natl Acad Sci USA 95:3603–3608

    PubMed  CAS  Google Scholar 

  215. Yanagi K, Mizuno T, You Z, Hanaoka F (2002) Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel intrinsic Cdt1 DNA binding activity. J Biol Chem 277:40871–40880

    PubMed  CAS  Google Scholar 

  216. Yoshida K, Inoue I (2004) Expression of MCM10 and TopBP1 is regulated by cell proliferation and UV irradiation via the E2F transcription factor. Oncogene 23:6250–6260

    PubMed  CAS  Google Scholar 

  217. You Z, Komamura Y, Ishimi Y (1999) Biochemical analysis of the intrinsic Mcm4-Mcm6-Mcm7 DNA helicase activity. Mol Cell Biol 19:8003–8015

    PubMed  CAS  Google Scholar 

  218. Young LS, Rickinson AB (2004) Epstein-Barr virus:40 years on. Nat Rev Cancer 4:757–768

    PubMed  CAS  Google Scholar 

  219. Zhong W, Feng H, Santiago FE, Kipreos ET (2003) CUL-4 ubiquitin ligase maintains genome stability by restraining DNA-replication licensing. Nature 423:885–889

    PubMed  CAS  Google Scholar 

  220. Zhu W, Chen Y, Dutta A (2004) Rereplication by depletion of geminin is seen regardless of p53 status and activates a G2/M checkpoint. Mol Cell Biol 24:7140–7150

    PubMed  CAS  Google Scholar 

  221. Zou L, Stillman B (1998) Formation of a preinitiation complex by S-phase cyclin CDK-dependent loading of Cdc45p onto chromatin. Science 280:593–596

    PubMed  CAS  Google Scholar 

  222. Zou L, Stillman B (2000) Assembly of a complex containing Cdc45p, replication protein A, and Mcm2p at replication origins controlled by S-phase cyclin-dependent kinases and Cdc7p-Dbf4p kinase. Mol Cell Biol 20:3086–3096

    PubMed  CAS  Google Scholar 

  223. Zou L, Mitchell J, Stillman B (1997) CDC45, a novel yeast gene that functions with the origin recognition complex and Mcm proteins in initiation of DNA replication. Mol Cell Biol 17:553–563

    PubMed  CAS  Google Scholar 

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  1. Biological and Biomedical Sciences Program, Harvard Medical School, 02115, Boston, MA, USA

    Jamie K. Teer & Anindya Dutta

  2. Dept. Of Biochemistry, University of Virginia, 22908, Charlottesville, VA, USA

    Jamie K. Teer & Anindya Dutta

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Teer, J.K., Dutta, A. Regulation of S Phase. In: Kaldis, P. (eds) Cell Cycle Regulation. Results and Problems in Cell Differentiation, vol 42. Springer, Berlin, Heidelberg. https://doi.org/10.1007/b137221

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