Advertisement

The Origin Recognition Complex: A Biochemical and Structural View

Chapter
First Online:
Part of the Subcellular Biochemistry book series (SCBI, volume 62)

Abstract

The origin recognition complex (ORC) was first discovered in the baker’s yeast in 1992. Identification of ORC opened up a path for subsequent molecular level investigations on how eukaryotic cells initiate and control genome duplication each cell cycle. Twenty years after the first biochemical isolation, ORC is now taking on a three-dimensional shape, although a very blurry shape at the moment, thanks to the recent electron microscopy and image reconstruction efforts. In this chapter, we outline the current biochemical knowledge about ORC from several eukaryotic systems, with emphasis on the most recent structural and biochemical studies. Despite many species-specific properties, an emerging consensus is that ORC is an ATP-dependent machine that recruits other key proteins to form pre-replicative complexes (pre-RCs) at many origins of DNA replication, enabling the subsequent initiation of DNA replication in S phase.

Keywords

DNA replication Replicative helicase loader Eukaryotes Replication initiators 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgements

Research in the authors’ labs is supported by grants from the National Institutes of Health, particularly CA13106 and GM45436.

References

  1. Abdurashidova G, Deganuto M, Klima R, Riva S, Biamonti G, Giacca M, Falaschi A (2000) Start sites of bidirectional DNA synthesis at the human lamin B2 origin. Science 287:2023–2026PubMedGoogle Scholar
  2. Abdurashidova G, Danailov MB, Ochem A, Triolo G, Djeliova V, Radulescu S, Vindigni A, Riva S, Falaschi A (2003) Localization of proteins bound to a replication origin of human DNA along the cell cycle. EMBO J 22:4294–4303PubMedGoogle Scholar
  3. Aggarwal BD, Calvi BR (2004) Chromatin regulates origin activity in Drosophila follicle cells. Nature 430:372–376PubMedGoogle Scholar
  4. 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 22:6115–6126PubMedGoogle Scholar
  5. Armache KJ, Garlick JD, Canzio D, Narlikar GJ, Kingston RE (2011) Structural basis of silencing: Sir3 BAH domain in complex with a nucleosome at 3.0 A resolution. Science 334:977–982PubMedGoogle Scholar
  6. Asano T, Makise M, Takehara M, Mizushima T (2007) Interaction between ORC and Cdt1p of Saccharomyces cerevisiae. FEMS Yeast Res 7:1256–1262PubMedGoogle Scholar
  7. Austin RJ, Orr-Weaver TL, Bell SP (1999) Drosophila ORC specifically binds to ACE3, an origin of DNA replication control element. Genes Dev 13:2639–2649PubMedGoogle Scholar
  8. Badugu R, Yoo Y, Singh PB, Kellum R (2005) Mutations in the heterochromatin protein 1 (HP1) hinge domain affect HP1 protein interactions and chromosomal distribution. Chromosoma 113:370–384PubMedGoogle Scholar
  9. Baldinger T, Gossen M (2009) Binding of Drosophila ORC proteins to anaphase chromosomes requires cessation of mitotic cyclin-dependent kinase activity. Mol Cell Biol 29:140–149PubMedGoogle Scholar
  10. Bartke T, Vermeulen M, Xhemalce B, Robson SC, Mann M, Kouzarides T (2010) Nucleosome-interacting proteins regulated by DNA and histone methylation. Cell 143:470–484PubMedGoogle Scholar
  11. Beall EL, Manak JR, Zhou S, Bell M, Lipsick JS, Botchan MR (2002) Role for a Drosophila Myb-containing protein complex in site-specific DNA replication. Nature 420:833–837PubMedGoogle Scholar
  12. Bell SP, Dutta A (2002) DNA replication in eukaryotic cells. Annu Rev Biochem 71:333–374PubMedGoogle Scholar
  13. Bell SP, Stillman B (1992) ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex. Nature 357:128–134PubMedGoogle Scholar
  14. Bell SP, Kobayashi R, Stillman B (1993) Yeast origin recognition complex functions in transcription silencing and DNA replication. Science 262:1844–1849PubMedGoogle Scholar
  15. Bell SP, Mitchell J, Leber J, Kobayashi R, Stillman B (1995) The multidomain structure of Orc1p reveals similarity to regulators of DNA replication and transcriptional silencing. Cell 83:563–568PubMedGoogle Scholar
  16. Berquist BR, DasSarma S (2003) An archaeal chromosomal autonomously replicating sequence element from an extreme halophile, Halobacterium sp. strain NRC-1. J Bacteriol 185:5959–5966PubMedGoogle Scholar
  17. Bielinsky AK, Gerbi SA (1998) Discrete start sites for DNA synthesis in the yeast ARS1 origin. Science 279:95–98PubMedGoogle Scholar
  18. Bielinsky AK, Gerbi SA (2001) Where it all starts: eukaryotic origins of DNA replication. J Cell Sci 114:643–651PubMedGoogle Scholar
  19. Bielinsky AK, Blitzblau H, Beall EL, Ezrokhi M, Smith HS, Botchan MR, Gerbi SA (2001) Origin recognition complex binding to a metazoan replication origin. Curr Biol 11:1427–1431PubMedGoogle Scholar
  20. Bosco G, Du W, Orr-Weaver TL (2001) DNA replication control through interaction of E2F-RB and the origin recognition complex. Nat Cell Biol 3:289–295PubMedGoogle Scholar
  21. Bose ME, McConnell KH, Gardner-Aukema KA, Muller U, Weinreich M, Keck JL, Fox CA (2004) The origin recognition complex and Sir4 protein recruit Sir1p to yeast silent chromatin through independent interactions requiring a common Sir1p domain. Mol Cell Biol 24:774–786PubMedGoogle Scholar
  22. Bowers JL, Randell JC, Chen S, Bell SP (2004) ATP hydrolysis by ORC catalyzes reiterative Mcm2-7 assembly at a defined origin of replication. Mol Cell 16:967–978PubMedGoogle Scholar
  23. Brewer BJ, Fangman WL (1987) The localization of replication origins on ARS plasmids in S. cerevisiae. Cell 51:463–471PubMedGoogle Scholar
  24. Calvi BR, Byrnes BA, Kolpakas AJ (2007) Conservation of epigenetic regulation, ORC binding and developmental timing of DNA replication origins in the genus Drosophila. Genetics 177:1291–1301PubMedGoogle Scholar
  25. Cao XQ, Zeng J, Yan H (2008) Structural properties of replication origins in yeast DNA sequences. Phys Biol 5:036012PubMedGoogle Scholar
  26. Capaldi SA, Berger JM (2004) Biochemical characterization of Cdc6/Orc1 binding to the replication origin of the euryarchaeon Methanothermobacter thermoautotrophicus. Nucleic Acids Res 32:4821–4832PubMedGoogle Scholar
  27. Chakraborty A, Shen Z, Prasanth SG (2011) “ORCanization” on heterochromatin: linking DNA replication initiation to chromatin organization. Epigenetics 6:665–670PubMedGoogle Scholar
  28. Chang F, May CD, Hoggard T, Miller J, Fox CA, Weinreich M (2011) High-resolution analysis of four efficient yeast replication origins reveals new insights into the ORC and putative MCM binding elements. Nucleic Acids Res 39:6523–6535PubMedGoogle Scholar
  29. Chastain PD 2nd, Bowers JL, Lee DG, Bell SP, Griffith JD (2004) Mapping subunit location on the Saccharomyces cerevisiae origin recognition complex free and bound to DNA using a novel nanoscale biopointer. J Biol Chem 279:36354–36362PubMedGoogle Scholar
  30. 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 98:10085–10089PubMedGoogle Scholar
  31. Chen S, Bell SP (2011) CDK prevents Mcm2-7 helicase loading by inhibiting Cdt1 interaction with Orc6. Genes Dev 25:363–372PubMedGoogle Scholar
  32. Chen S, de Vries MA, Bell SP (2007) Orc6 is required for dynamic recruitment of Cdt1 during repeated Mcm2-7 loading. Genes Dev 21:2897–2907PubMedGoogle Scholar
  33. Chen Z, Speck C, Wendel P, Tang C, Stillman B, Li H (2008) The architecture of the DNA replication origin recognition complex in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 105:10326–10331PubMedGoogle Scholar
  34. Chesnokov I, Gossen M, Remus D, Botchan M (1999) Assembly of functionally active Drosophila origin recognition complex from recombinant proteins. Genes Dev 13:1289–1296PubMedGoogle Scholar
  35. Chesnokov I, Remus D, Botchan M (2001) Functional analysis of mutant and wild-type Drosophila origin recognition complex. Proc Natl Acad Sci USA 98:11997–12002PubMedGoogle Scholar
  36. Chesnokov IN, Chesnokova ON, Botchan M (2003) A cytokinetic function of Drosophila ORC6 protein resides in a domain distinct from its replication activity. Proc Natl Acad Sci USA 100:9150–9155PubMedGoogle Scholar
  37. Chuang RY, Kelly TJ (1999) The fission yeast homologue of Orc4p binds to replication origin DNA via multiple AT-hooks. Proc Natl Acad Sci USA 96:2656–2661PubMedGoogle Scholar
  38. Chuang RY, Chretien L, Dai J, Kelly TJ (2002) Purification and characterization of the Schizosaccharomyces pombe origin recognition complex: interaction with origin DNA and Cdc18 protein. J Biol Chem 277:16920–16927PubMedGoogle Scholar
  39. Clarey MG, Erzberger JP, Grob P, Leschziner AE, Berger JM, Nogales E, Botchan M (2006) Nucleotide-dependent conformational changes in the DnaA-like core of the origin recognition complex. Nat Struct Mol Biol 13:684–690PubMedGoogle Scholar
  40. 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 379:180–182PubMedGoogle Scholar
  41. Craig JM, Earle E, Canham P, Wong LH, Anderson M, Choo KH (2003) Analysis of mammalian proteins involved in chromatin modification reveals new metaphase centromeric proteins and distinct chromosomal distribution patterns. Hum Mol Genet 12:3109–3121PubMedGoogle Scholar
  42. Cvetic C, Walter JC (2005) Eukaryotic origins of DNA replication: could you please be more specific? Semin Cell Dev Biol 16:343–353PubMedGoogle Scholar
  43. DePamphilis ML (2003) The ‘ORC cycle’: a novel pathway for regulating eukaryotic DNA replication. Gene 310:1–15PubMedGoogle Scholar
  44. DePamphilis ML (2005) Cell cycle dependent regulation of the origin recognition complex. Cell Cycle 4:70–79PubMedGoogle Scholar
  45. DePamphilis ML, Blow JJ, Ghosh S, Saha T, Noguchi K, Vassilev A (2006) Regulating the licensing of DNA replication origins in metazoa. Curr Opin Cell Biol 18:231–239PubMedGoogle Scholar
  46. Deshpande AM, Newlon CS (1992) The ARS consensus sequence is required for chromosomal origin function in Saccharomyces cerevisiae. Mol Cell Biol 12:4305–4313PubMedGoogle Scholar
  47. Dhar SK, Dutta A (2000) Identification and characterization of the human ORC6 homolog. J Biol Chem 275:34983–34988PubMedGoogle Scholar
  48. Dhar SK, Delmolino L, Dutta A (2001a) Architecture of the human origin recognition complex. J Biol Chem 276:29067–29071PubMedGoogle Scholar
  49. 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 106:287–296PubMedGoogle Scholar
  50. Diffley JF, Labib K (2002) The chromosome replication cycle. J Cell Sci 115:869–872PubMedGoogle Scholar
  51. Drury LS, Perkins G, Diffley JF (1997) The Cdc4/34/53 pathway targets Cdc6p for proteolysis in budding yeast. EMBO J 16:5966–5976PubMedGoogle Scholar
  52. Drury LS, Perkins G, Diffley JF (2000) The cyclin-dependent kinase Cdc28p regulates distinct modes of Cdc6p proteolysis during the budding yeast cell cycle. Curr Biol 10:231–240PubMedGoogle Scholar
  53. Dueber EL, Corn JE, Bell SD, Berger JM (2007) Replication origin recognition and deformation by a heterodimeric archaeal Orc1 complex. Science 317:1210–1213PubMedGoogle Scholar
  54. Dueber EC, Costa A, Corn JE, Bell SD, Berger JM (2011) Molecular determinants of origin discrimination by Orc1 initiators in archaea. Nucleic Acids Res 39:3621–3631PubMedGoogle Scholar
  55. Duncker BP, Pasero P, Braguglia D, Heun P, Weinreich M, Gasser SM (1999) Cyclin B-cdk1 kinase stimulates ORC- and Cdc6-independent steps of semiconservative plasmid replication in yeast nuclear extracts. Mol Cell Biol 19:1226–1241PubMedGoogle Scholar
  56. Duncker BP, Chesnokov IN, McConkey BJ (2009) The origin recognition complex protein family. Genome Biol 10:214PubMedGoogle Scholar
  57. Eaton ML, Galani K, Kang S, Bell SP, MacAlpine DM (2010) Conserved nucleosome positioning defines replication origins. Genes Dev 24:748–753PubMedGoogle Scholar
  58. Eaton ML, Prinz JA, MacAlpine HK, Tretyakov G, Kharchenko PV, MacAlpine DM (2011) Chromatin signatures of the Drosophila replication program. Genome Res 21:164–174PubMedGoogle Scholar
  59. Ehrentraut S, Hassler M, Oppikofer M, Kueng S, Weber JM, Mueller JW, Gasser SM, Ladurner AG, Ehrenhofer-Murray AE (2011) Structural basis for the role of the Sir3 AAA + domain in silencing: interaction with Sir4 and unmethylated histone H3K79. Genes Dev 25:1835–1846PubMedGoogle Scholar
  60. Evrin C, Clarke P, Zech J, Lurz R, Sun J, Uhle S, Li H, Stillman B, Speck C (2009) A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication. Proc Natl Acad Sci USA 106:20240–20245PubMedGoogle Scholar
  61. Falaschi A, Abdurashidova G, Sandoval O, Radulescu S, Biamonti G, Riva S (2007) Molecular and structural transactions at human DNA replication origins. Cell Cycle 6:1705–1712PubMedGoogle Scholar
  62. Fox CA, Ehrenhofer-Murray AE, Loo S, Rine J (1997) The origin recognition complex, SIR1, and the S phase requirement for silencing. Science 276:1547–1551PubMedGoogle Scholar
  63. Gaczynska M, Osmulski PA, Jiang Y, Lee JK, Bermudez V, Hurwitz J (2004) Atomic force microscopic analysis of the binding of the Schizosaccharomyces pombe origin recognition complex and the spOrc4 protein with origin DNA. Proc Natl Acad Sci USA 101:17952–17957PubMedGoogle Scholar
  64. Gardner KA, Rine J, Fox CA (1999) A region of the Sir1 protein dedicated to recognition of a silencer and required for interaction with the Orc1 protein in Saccharomyces cerevisiae. Genetics 151:31–44PubMedGoogle Scholar
  65. Gaudier M, Schuwirth BS, Westcott SL, Wigley DB (2007) Structural basis of DNA replication origin recognition by an ORC protein. Science 317:1213–1216PubMedGoogle Scholar
  66. Gavin KA, Hidaka M, Stillman B (1995) Conserved initiator proteins in eukaryotes. Science 270:1667–1671PubMedGoogle Scholar
  67. Georlette D, Ahn S, MacAlpine DM, Cheung E, Lewis PW, Beall EL, Bell SP, Speed T, Manak JR, Botchan MR (2007) Genomic profiling and expression studies reveal both positive and negative activities for the Drosophila Myb MuvB/dREAM complex in proliferating cells. Genes Dev 21:2880–2896PubMedGoogle Scholar
  68. Ghosh S, Vassilev AP, Zhang J, Zhao Y, DePamphilis ML (2011) Assembly of the human origin recognition complex occurs through independent nuclear localization of its components. J Biol Chem 286:23831–23841PubMedGoogle Scholar
  69. Gibson DG, Bell SP, Aparicio OM (2006) Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae. Genes Cells 11:557–573PubMedGoogle Scholar
  70. Gilbert DM (1998) Replication origins in yeast versus metazoa: separation of the haves and the have nots. Curr Opin Genet Dev 8:194–199PubMedGoogle Scholar
  71. Gilbert DM (2010) Evaluating genome-scale approaches to eukaryotic DNA replication. Nat Rev Genet 11:673–684PubMedGoogle Scholar
  72. Giordano-Coltart J, Ying CY, Gautier J, Hurwitz J (2005) Studies of the properties of human origin recognition complex and its Walker A motif mutants. Proc Natl Acad Sci USA 102:69–74PubMedGoogle Scholar
  73. Gossen M, Pak DT, Hansen SK, Acharya JK, Botchan MR (1995) A Drosophila homolog of the yeast origin recognition complex. Science 270:1674–1677PubMedGoogle Scholar
  74. Grainge I, Scaife S, Wigley DB (2003) Biochemical analysis of components of the pre-replication complex of Archaeoglobus fulgidus. Nucleic Acids Res 31:4888–4898PubMedGoogle Scholar
  75. Harland RM, Laskey RA (1980) Regulated replication of DNA microinjected into eggs of Xenopus laevis. Cell 21:761–771PubMedGoogle Scholar
  76. Hartl T, Boswell C, Orr-Weaver TL, Bosco G (2007) Developmentally regulated histone modifications in Drosophila follicle cells: initiation of gene amplification is associated with histone H3 and H4 hyperacetylation and H1 phosphorylation. Chromosoma 116:197–214PubMedGoogle Scholar
  77. Hemerly AS, Prasanth SG, Siddiqui K, Stillman B (2009) Orc1 controls centriole and centrosome copy number in human cells. Science 323:789–793PubMedGoogle Scholar
  78. Hickman MA, Rusche LN (2010) Transcriptional silencing functions of the yeast protein Orc1/Sir3 subfunctionalized after gene duplication. Proc Natl Acad Sci USA 107:19384–19389PubMedGoogle Scholar
  79. Hou Z, Bernstein DA, Fox CA, Keck JL (2005) Structural basis of the Sir1-origin recognition complex interaction in transcriptional silencing. Proc Natl Acad Sci USA 102:8489–8494PubMedGoogle Scholar
  80. Houchens CR, Lu W, Chuang RY, Frattini MG, Fuller A, Simancek P, Kelly TJ (2008) Multiple mechanisms contribute to Schizosaccharomyces pombe origin recognition complex-DNA interactions. J Biol Chem 283:30216–30224PubMedGoogle Scholar
  81. Huang RY, Kowalski D (1993) A DNA unwinding element and an ARS consensus comprise a replication origin within a yeast chromosome. EMBO J 12:4521–4531PubMedGoogle Scholar
  82. Huang DW, Fanti L, Pak DT, Botchan MR, Pimpinelli S, Kellum R (1998) Distinct cytoplasmic and nuclear fractions of Drosophila heterochromatin protein 1: their phosphorylation levels and associations with origin recognition complex proteins. J Cell Biol 142:307–318PubMedGoogle Scholar
  83. Huijbregts RP, Svitin A, Stinnett MW, Renfrow MB, Chesnokov I (2009) Drosophila Orc6 facilitates GTPase activity and filament formation of the septin complex. Mol Biol Cell 20:270–281PubMedGoogle Scholar
  84. Julien MD, Polonskaya Z, Hearing J (2004) Protein and sequence requirements for the recruitment of the human origin recognition complex to the latent cycle origin of DNA replication of Epstein-Barr virus oriP. Virology 326:317–328PubMedGoogle Scholar
  85. Karnani N, Taylor CM, Malhotra A, Dutta A (2010) Genomic study of replication initiation in human chromosomes reveals the influence of transcription regulation and chromatin structure on origin selection. Mol Biol Cell 21:393–404PubMedGoogle Scholar
  86. Kawakami H, Katayama T (2010) DnaA, ORC, and Cdc6: similarity beyond the domains of life and diversity. Biochem Cell Biol 88:49–62PubMedGoogle Scholar
  87. 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 19:1681–1690PubMedGoogle Scholar
  88. Kelly TJ, Martin GS, Forsburg SL, Stephen RJ, Russo A, Nurse P (1993) The fission yeast cdc18 + gene product couples S phase to START and mitosis. Cell 74:371–382PubMedGoogle Scholar
  89. Kim JC, Orr-Weaver TL (2011) Analysis of a Drosophila amplicon in follicle cells highlights the diversity of metazoan replication origins. Proc Natl Acad Sci USA 108:16681–16686PubMedGoogle Scholar
  90. Kim JC, Nordman J, Xie F, Kashevsky H, Eng T, Li S, MacAlpine DM, Orr-Weaver TL (2011) Integrative analysis of gene amplification in Drosophila follicle cells: parameters of origin activation and repression. Genes Dev 25:1384–1398PubMedGoogle Scholar
  91. Klemm RD, Bell SP (2001) ATP bound to the origin recognition complex is important for preRC formation. Proc Natl Acad Sci USA 98:8361–8367PubMedGoogle Scholar
  92. Klemm RD, Austin RJ, Bell SP (1997) Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex. Cell 88:493–502PubMedGoogle Scholar
  93. Kong D, DePamphilis ML (2002) Site-specific ORC binding, pre-replication complex assembly and DNA synthesis at Schizosaccharomyces pombe replication origins. EMBO J 21:5567–5576PubMedGoogle Scholar
  94. Kreitz S, Ritzi M, Baack M, Knippers R (2001) The human origin recognition complex protein 1 dissociates from chromatin during S phase in HeLa cells. J Biol Chem 276:6337–6342PubMedGoogle Scholar
  95. Ladenburger EM, Keller C, Knippers R (2002) Identification of a binding region for human origin recognition complex proteins 1 and 2 that coincides with an origin of DNA replication. Mol Cell Biol 22:1036–1048PubMedGoogle Scholar
  96. Lee DG, Bell SP (1997) Architecture of the yeast origin recognition complex bound to origins of DNA replication. Mol Cell Biol 17:7159–7168PubMedGoogle Scholar
  97. Lee DG, Bell SP (2000) ATPase switches controlling DNA replication initiation. Curr Opin Cell Biol 12:280–285PubMedGoogle Scholar
  98. Lee DG, Makhov AM, Klemm RD, Griffith JD, Bell SP (2000) Regulation of origin recognition complex conformation and ATPase activity: differential effects of single-stranded and double-stranded DNA binding. EMBO J 19:4774–4782PubMedGoogle Scholar
  99. 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 98:13589–13594PubMedGoogle Scholar
  100. Liang C, Weinreich M, Stillman B (1995) ORC and Cdc6p interact and determine the frequency of initiation of DNA replication in the genome. Cell 81:667–676PubMedGoogle Scholar
  101. Lidonnici MR, Rossi R, Paixao S, Mendoza-Maldonado R, Paolinelli R, Arcangeli C, Giacca M, Biamonti G, Montecucco A (2004) Subnuclear distribution of the largest subunit of the human origin recognition complex during the cell cycle. J Cell Sci 117:5221–5231PubMedGoogle Scholar
  102. Lipford JR, Bell SP (2001) Nucleosomes positioned by ORC facilitate the initiation of DNA replication. Mol Cell 7:21–30PubMedGoogle Scholar
  103. Liu S, Balasov M, Wang H, Wu L, Chesnokov IN, Liu Y (2011) Structural analysis of human Orc6 protein reveals a homology with transcription factor TFIIB. Proc Natl Acad Sci USA 108:7373–7378PubMedGoogle Scholar
  104. Liu J, McConnell K, Dixon M, Calvi BR (2012) Analysis of model replication origins in Drosophila reveals new aspects of the chromatin landscape and its relationship to origin activity and the prereplicative complex. Mol Biol Cell 23:200–212PubMedGoogle Scholar
  105. Loupart ML, Krause SA, Heck MS (2000) Aberrant replication timing induces defective chromosome condensation in Drosophila ORC2 mutants. Curr Biol 10:1547–1556PubMedGoogle Scholar
  106. MacAlpine DM, Rodriguez HK, Bell SP (2004) Coordination of replication and transcription along a Drosophila chromosome. Genes Dev 18:3094–3105PubMedGoogle Scholar
  107. MacAlpine HK, Gordan R, Powell SK, Hartemink AJ, MacAlpine DM (2010) Drosophila ORC localizes to open chromatin and marks sites of cohesin complex loading. Genome Res 20:201–211PubMedGoogle Scholar
  108. Makise M, Takehara M, Kuniyasu A, Matsui N, Nakayama H, Mizushima T (2009) Linkage between phosphorylation of the origin recognition complex and its ATP binding activity in Saccharomyces cerevisiae. J Biol Chem 284:3396–3407PubMedGoogle Scholar
  109. Marahrens Y, Stillman B (1992) A yeast chromosomal origin of DNA replication defined by multiple functional elements. Science 255:817–823PubMedGoogle Scholar
  110. Matsuda K, Makise M, Sueyasu Y, Takehara M, Asano T, Mizushima T (2007) Yeast two-hybrid analysis of the origin recognition complex of Saccharomyces cerevisiae: interaction between subunits and identification of binding proteins. FEMS Yeast Res 7:1263–1269PubMedGoogle Scholar
  111. Mendez J, Stillman B (2003) Perpetuating the double helix: molecular machines at eukaryotic DNA replication origins. Bioessays 25:1158–1167PubMedGoogle Scholar
  112. 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 9:481–491PubMedGoogle Scholar
  113. 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 96:12367–12372PubMedGoogle Scholar
  114. Muller P, Park S, Shor E, Huebert DJ, Warren CL, Ansari AZ, Weinreich M, Eaton ML, MacAlpine DM, Fox CA (2010) The conserved bromo-adjacent homology domain of yeast Orc1 functions in the selection of DNA replication origins within chromatin. Genes Dev 24:1418–1433PubMedGoogle Scholar
  115. Natale DA, Umek RM, Kowalski D (1993) Ease of DNA unwinding is a conserved property of yeast replication origins. Nucleic Acids Res 21:555–560PubMedGoogle Scholar
  116. Nguyen VQ, Co C, Li JJ (2001) Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms. Nature 411:1068–1073PubMedGoogle Scholar
  117. Nishitani H, Nurse P (1997) The cdc18 protein initiates DNA replication in fission yeast. Prog Cell Cycle Res 3:135–142PubMedGoogle Scholar
  118. Noguchi K, Vassilev A, Ghosh S, Yates JL, DePamphilis ML (2006) The BAH domain facilitates the ability of human Orc1 protein to activate replication origins in vivo. EMBO J 25:5372–5382PubMedGoogle Scholar
  119. Norseen J, Thomae A, Sridharan V, Aiyar A, Schepers A, Lieberman PM (2008) RNA-dependent recruitment of the origin recognition complex. EMBO J 27:3024–3035PubMedGoogle Scholar
  120. Ogawa Y, Takahashi T, Masukata H (1999) Association of fission yeast Orp1 and Mcm6 proteins with chromosomal replication origins. Mol Cell Biol 19:7228–7236PubMedGoogle Scholar
  121. Ozaydin B, Rine J (2010) Expanded roles of the origin recognition complex in the architecture and function of silenced chromatin in Saccharomyces cerevisiae. Mol Cell Biol 30:626–639PubMedGoogle Scholar
  122. Pak DT, Pflumm M, Chesnokov I, Huang DW, Kellum R, Marr J, Romanowski P, Botchan MR (1997) Association of the origin recognition complex with heterochromatin and HP1 in higher eukaryotes. Cell 91:311–323PubMedGoogle Scholar
  123. Perkins G, Drury LS, Diffley JF (2001) Separate SCF(CDC4) recognition elements target Cdc6 for proteolysis in S phase and mitosis. EMBO J 20:4836–4845PubMedGoogle Scholar
  124. Pflumm MF, Botchan MR (2001) Orc mutants arrest in metaphase with abnormally condensed chromosomes. Development 128:1697–1707PubMedGoogle Scholar
  125. Piatti S, Bohm T, Cocker JH, Diffley JF, Nasmyth K (1996) Activation of S-phase-promoting CDKs in late G1 defines a “point of no return” after which Cdc6 synthesis cannot promote DNA replication in yeast. Genes Dev 10:1516–1531PubMedGoogle Scholar
  126. Pillus L, Rine J (1989) Epigenetic inheritance of transcriptional states in S. cerevisiae. Cell 59:637–647PubMedGoogle Scholar
  127. Pillus L, Rine J (2004) SIR1 and the origin of epigenetic states in Saccharomyces cerevisiae. Cold Spring Harb Symp Quant Biol 69:259–265PubMedGoogle Scholar
  128. Prasanth SG, Prasanth KV, Stillman B (2002) Orc6 involved in DNA replication, chromosome segregation, and cytokinesis. Science 297:1026–1031PubMedGoogle Scholar
  129. Prasanth SG, Prasanth KV, Siddiqui K, Spector DL, Stillman B (2004) Human Orc2 localizes to centrosomes, centromeres and heterochromatin during chromosome inheritance. EMBO J 23:2651–2663PubMedGoogle Scholar
  130. Prasanth SG, Shen Z, Prasanth KV, Stillman B (2010) Human origin recognition complex is essential for HP1 binding to chromatin and heterochromatin organization. Proc Natl Acad Sci USA 107:15093–15098PubMedGoogle Scholar
  131. Randell JC, Bowers JL, Rodriguez HK, Bell SP (2006) Sequential ATP hydrolysis by Cdc6 and ORC directs loading of the Mcm2-7 helicase. Mol Cell 21:29–39PubMedGoogle Scholar
  132. Ranjan A, Gossen M (2006) A structural role for ATP in the formation and stability of the human origin recognition complex. Proc Natl Acad Sci USA 103:4864–4869PubMedGoogle Scholar
  133. Rao H, Stillman B (1995) The origin recognition complex interacts with a bipartite DNA binding site within yeast replicators. Proc Natl Acad Sci USA 92:2224–2228PubMedGoogle Scholar
  134. Rao H, Marahrens Y, Stillman B (1994) Functional conservation of multiple elements in yeast chromosomal replicators. Mol Cell Biol 14:7643–7651PubMedGoogle Scholar
  135. Remus D, Beall EL, Botchan MR (2004) DNA topology, not DNA sequence, is a critical determinant for Drosophila ORC-DNA binding. EMBO J 23:897–907PubMedGoogle Scholar
  136. Remus D, Blanchette M, Rio DC, Botchan MR (2005) CDK phosphorylation inhibits the DNA-binding and ATP-hydrolysis activities of the Drosophila origin recognition complex. J Biol Chem 280:39740–39751PubMedGoogle Scholar
  137. Remus D, Beuron F, Tolun G, Griffith JD, Morris EP, Diffley JF (2009) Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing. Cell 139:719–730PubMedGoogle Scholar
  138. Romero J, Lee H (2008) Asymmetric bidirectional replication at the human DBF4 origin. Nat Struct Mol Biol 15:722–729PubMedGoogle Scholar
  139. 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 14:2631–2641PubMedGoogle Scholar
  140. Royzman I, Austin RJ, Bosco G, Bell SP, Orr-Weaver TL (1999) ORC localization in Drosophila follicle cells and the effects of mutations in dE2F and dDP. Genes Dev 13:827–840PubMedGoogle Scholar
  141. Ryba T, Hiratani I, Lu J, Itoh M, Kulik M, Zhang J, Schulz TC, Robins AJ, Dalton S, Gilbert DM (2010) Evolutionarily conserved replication timing profiles predict long-range chromatin interactions and distinguish closely related cell types. Genome Res 20:761–770PubMedGoogle Scholar
  142. Santocanale C, Diffley JF (1996) ORC- and Cdc6-dependent complexes at active and inactive chromosomal replication origins in Saccharomyces cerevisiae. EMBO J 15:6671–6679PubMedGoogle Scholar
  143. Sasaki T, Gilbert DM (2007) The many faces of the origin recognition complex. Curr Opin Cell Biol 19:337–343PubMedGoogle Scholar
  144. Scholefield G, Veening JW, Murray H (2011) DnaA and ORC: more than DNA replication initiators. Trends Cell Biol 21:188–194PubMedGoogle Scholar
  145. Shareef MM, King C, Damaj M, Badagu R, Huang DW, Kellum R (2001) Drosophila heterochromatin protein 1 (HP1)/origin recognition complex (ORC) protein is associated with HP1 and ORC and functions in heterochromatin-induced silencing. Mol Biol Cell 12:1671–1685PubMedGoogle Scholar
  146. Shareef MM, Badugu R, Kellum R (2003) HP1/ORC complex and heterochromatin assembly. Genetica 117:127–134PubMedGoogle Scholar
  147. Shen Z, Sathyan KM, Geng Y, Zheng R, Chakraborty A, Freeman B, Wang F, Prasanth KV, Prasanth SG (2010) A WD-repeat protein stabilizes ORC binding to chromatin. Mol Cell 40:99–111PubMedGoogle Scholar
  148. Sher N, Bell GW, Li S, Nordman J, Eng T, Eaton ML, Macalpine DM, Orr-Weaver TL (2012) Developmental control of gene copy number by repression of replication initiation and fork progression. Genome Res 22:64–75PubMedGoogle Scholar
  149. Siddiqui K, Stillman B (2007) ATP-dependent assembly of the human origin recognition complex. J Biol Chem 282:32370–32383PubMedGoogle Scholar
  150. Speck C, Stillman B (2007) Cdc6 ATPase activity regulates ORC x Cdc6 stability and the selection of specific DNA sequences as origins of DNA replication. J Biol Chem 282:11705–11714PubMedGoogle Scholar
  151. Speck C, Chen Z, Li H, Stillman B (2005) ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA. Nat Struct Mol Biol 12:965–971PubMedGoogle Scholar
  152. Spradling AC (1999) ORC binding, gene amplification, and the nature of metazoan replication origins. Genes Dev 13:2619–2623PubMedGoogle Scholar
  153. Stefanovic D, Stanojcic S, Vindigni A, Ochem A, Falaschi A (2003) In vitro protein-DNA interactions at the human lamin B2 replication origin. J Biol Chem 278:42737–42743PubMedGoogle Scholar
  154. Sun J, Kawakami H, Zech J, Speck C, Stillman B, Li H (2012) Cdc6-induced conformational changes in ORC bound to origin DNA revealed by cryo-electron microscopy. Structure 20:534–544PubMedGoogle Scholar
  155. Tada S, Kundu LR, Enomoto T (2008) Insight into initiator-DNA interactions: a lesson from the archaeal ORC. Bioessays 30:208–211PubMedGoogle Scholar
  156. Takahashi T, Ohara E, Nishitani H, Masukata H (2003) Multiple ORC-binding sites are required for efficient MCM loading and origin firing in fission yeast. EMBO J 22:964–974PubMedGoogle Scholar
  157. Takara TJ, Bell SP (2011) Multiple Cdt1 molecules act at each origin to load replication-competent Mcm2-7 helicases. EMBO J 30:4885–4896PubMedGoogle Scholar
  158. Takehara M, Makise M, Takenaka H, Asano T, Mizushima T (2008) Analysis of mutant origin recognition complex with reduced ATPase activity in vivo and in vitro. Biochem J 413:535–543PubMedGoogle Scholar
  159. Takenaka H, Makise M, Kuwae W, Takahashi N, Tsuchiya T, Mizushima T (2004) ADP-binding to origin recognition complex of Saccharomyces cerevisiae. J Mol Biol 340:29–37PubMedGoogle Scholar
  160. 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 278:41528–41534PubMedGoogle Scholar
  161. Theis JF, Newlon CS (1994) Domain B of ARS307 contains two functional elements and contributes to chromosomal replication origin function. Mol Cell Biol 14:7652–7659PubMedGoogle Scholar
  162. Theis JF, Newlon CS (2001) Two compound replication origins in Saccharomyces cerevisiae contain redundant origin recognition complex binding sites. Mol Cell Biol 21:2790–2801PubMedGoogle Scholar
  163. Thomae AW, Pich D, Brocher J, Spindler MP, Berens C, Hock R, Hammerschmidt W, Schepers A (2008) Interaction between HMGA1a and the origin recognition complex creates site-specific replication origins. Proc Natl Acad Sci USA 105:1692–1697PubMedGoogle Scholar
  164. Triolo T, Sternglanz R (1996) Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing. Nature 381:251–253PubMedGoogle Scholar
  165. 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 273:32421–32429PubMedGoogle Scholar
  166. Van Houten JV, Newlon CS (1990) Mutational analysis of the consensus sequence of a replication origin from yeast chromosome III. Mol Cell Biol 10:3917–3925PubMedGoogle Scholar
  167. Vashee S, Simancek P, Challberg MD, Kelly TJ (2001) Assembly of the human origin recognition complex. J Biol Chem 276:26666–26673PubMedGoogle Scholar
  168. Vashee S, Cvetic C, Lu W, Simancek P, Kelly TJ, Walter JC (2003) Sequence-independent DNA binding and replication initiation by the human origin recognition complex. Genes Dev 17:1894–1908PubMedGoogle Scholar
  169. Vermeulen M, Eberl HC, Matarese F, Marks H, Denissov S, Butter F, Lee KK, Olsen JV, Hyman AA, Stunnenberg HG, Mann M (2010) Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers. Cell 142:967–980PubMedGoogle Scholar
  170. Wallace JA, Orr-Weaver TL (2005) Replication of heterochromatin: insights into mechanisms of epigenetic inheritance. Chromosoma 114:389–402PubMedGoogle Scholar
  171. Weber JM, Irlbacher H, Ehrenhofer-Murray AE (2008) Control of replication initiation by the Sum1/Rfm1/Hst1 histone deacetylase. BMC Mol Biol 9:100PubMedGoogle Scholar
  172. Weinreich M, Liang C, Chen HH, Stillman B (2001) Binding of cyclin-dependent kinases to ORC and Cdc6p regulates the chromosome replication cycle. Proc Natl Acad Sci USA 98:11211–11217PubMedGoogle Scholar
  173. Wigley DB (2009) ORC proteins: marking the start. Curr Opin Struct Biol 19:72–78PubMedGoogle Scholar
  174. Wilmes GM, Bell SP (2002) The B2 element of the Saccharomyces cerevisiae ARS1 origin of replication requires specific sequences to facilitate pre-RC formation. Proc Natl Acad Sci USA 99:101–106PubMedGoogle Scholar
  175. 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 18:981–991PubMedGoogle Scholar
  176. Wu PY, Nurse P (2009) Establishing the program of origin firing during S phase in fission yeast. Cell 136:852–864PubMedGoogle Scholar
  177. Xie F, Orr-Weaver TL (2008) Isolation of a Drosophila amplification origin developmentally activated by transcription. Proc Natl Acad Sci USA 105:9651–9656PubMedGoogle Scholar
  178. Zhang Z, Hayashi MK, Merkel O, Stillman B, Xu RM (2002) Structure and function of the BAH-containing domain of Orc1p in epigenetic silencing. EMBO J 21:4600–4611PubMedGoogle Scholar
  179. 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 20:3086–3096PubMedGoogle Scholar
  180. Zou Y, Yu Q, Bi X (2006) Asymmetric positioning of nucleosomes and directional establishment of transcriptionally silent chromatin by Saccharomyces cerevisiae silencers. Mol Cell Biol 26:7806–7819PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  1. 1.Department of Biochemistry and Cell BiologyStony Brook UniversityStony BrookUSA
  2. 2.Biology DepartmentBrookhaven National LaboratoryUptonUSA
  3. 3.Cold Spring Harbor LaboratoryCold Spring HarborUSA

Personalised recommendations

Cite chapter

Buy options