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Chromosoma

, Volume 124, Issue 3, pp 309–321 | Cite as

Evolutionary conservation of the CDK targets in eukaryotic DNA replication initiation

  • Philip ZegermanEmail author
Review

Abstract

A fundamental requirement for all organisms is the faithful duplication and transmission of the genetic material. Failure to accurately copy and segregate the genome during cell division leads to loss of genetic information and chromosomal abnormalities. Such genome instability is the hallmark of the earliest stages of tumour formation. Cyclin-dependent kinase (CDK) plays a vital role in regulating the duplication of the genome within the eukaryotic cell cycle. Importantly, this kinase is deregulated in many cancer types and is an emerging target of chemotherapeutics. In this review, I will consider recent advances concerning the role of CDK in replication initiation across eukaryotes. The implications for strict CDK-dependent regulation of genome duplication in the context of the cell cycle will be discussed.

Keywords

Replication Initiation Origin Recognition Complex Origin Firing RecQ4 Helicase Rothmund Thomson Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

I apologise for any omissions due to space limitations and I am grateful to anonymous referees for their comments. I thank Vincent Gaggioli for critical reading of the manuscript and Max Telford and the Genome Institute at Washington University for access to the Priapulus caudatus genome sequence. PZ is supported Worldwide Cancer Research (AICR) 10-0908.

References

  1. Abe T, Yoshimura A, Hosono Y, Tada S, Seki M, Enomoto T (2011) The N-terminal region of RECQL4 lacking the helicase domain is both essential and sufficient for the viability of vertebrate cells. Role of the N-terminal region of RECQL4 in cells. Biochim Biophys Acta 1813(3):473–479PubMedGoogle Scholar
  2. Aparicio OM (2013) Location, location, location: it’s all in the timing for replication origins. Genes Dev 27(2):117–128PubMedCentralPubMedGoogle Scholar
  3. Araki H (2010) Cyclin-dependent kinase-dependent initiation of chromosomal DNA replication. Curr Opin Cell Biol 22(6):766–771PubMedGoogle Scholar
  4. Araki H (2011) Initiation of chromosomal DNA replication in eukaryotic cells; contribution of yeast genetics to the elucidation. Genes Genet Syst 86(3):141–149PubMedGoogle Scholar
  5. Arias EE, Walter JC (2007) Strength in numbers: preventing rereplication via multiple mechanisms in eukaryotic cells. Genes Dev 21(5):497–518PubMedGoogle Scholar
  6. Aves SJ, Liu Y, Richards TA (2012) Evolutionary diversification of eukaryotic DNA replication machinery. Subcell Biochem 62:19–35PubMedGoogle Scholar
  7. Balestrini A, Cosentino C, Errico A, Garner E, Costanzo V (2010) GEMC1 is a TopBP1-interacting protein required for chromosomal DNA replication. Nat Cell Biol 12(5):484–491PubMedCentralPubMedGoogle Scholar
  8. Bell SD (2012) Archaeal orc1/cdc6 proteins. Subcell Biochem 62:59–69PubMedGoogle Scholar
  9. Bell SD, Botchan MR (2013) The minichromosome maintenance replicative helicase. Cold Spring Harb Perspect Biol 5(11):a012807PubMedGoogle Scholar
  10. Bell SP, Kaguni JM (2013) Helicase loading at chromosomal origins of replication. Cold Spring Harb Perspect Biol 5(6)Google Scholar
  11. Blow JJ, Dutta A (2005) Preventing re-replication of chromosomal DNA. Nat Rev Mol Cell Biol 6(6):476–486PubMedCentralPubMedGoogle Scholar
  12. Blow JJ, Laskey RA (1988) A role for the nuclear envelope in controlling DNA replication within the cell cycle. Nature 332(6164):546–548PubMedGoogle Scholar
  13. Blow JJ, Ge XQ, Jackson DA (2011) How dormant origins promote complete genome replication. Trends Biochem Sci 36(8):405–414PubMedCentralPubMedGoogle Scholar
  14. Boos D, Sanchez-Pulido L, Rappas M, Pearl LH, Oliver AW, Ponting CP, Diffley JF (2011) Regulation of DNA replication through Sld3-Dpb11 interaction is conserved from yeast to humans. Curr Biol 21(13):1152–1157PubMedGoogle Scholar
  15. Boos D, Frigola J, Diffley JF (2012) Activation of the replicative DNA helicase: breaking up is hard to do. Curr Opin Cell Biol 24(3):423–430PubMedGoogle Scholar
  16. Boos D, Yekezare M, Diffley JF (2013) Identification of a heteromeric complex that promotes DNA replication origin firing in human cells. Science 340(6135):981–984PubMedGoogle Scholar
  17. Boye E, Lobner-Olesen A, Skarstad K (2000) Limiting DNA replication to once and only once. EMBO Rep 1(6):479–483PubMedCentralPubMedGoogle Scholar
  18. Brummer A, Salazar C, Zinzalla V, Alberghina L, Hofer T (2010) Mathematical modelling of DNA replication reveals a trade-off between coherence of origin activation and robustness against rereplication. PLoS Comput Biol 6(5):e1000783PubMedCentralPubMedGoogle Scholar
  19. Capp C, Wu J, Hsieh TS (2009) Drosophila RecQ4 has a 3′-5′ DNA helicase activity that is essential for viability. J Biol Chem 284(45):30845–30852PubMedCentralPubMedGoogle Scholar
  20. Chowdhury A, Liu G, Kemp M, Chen X, Katrangi N, Myers S, Ghosh M, Yao J, Gao Y, Bubulya P, Leffak M (2010) The DNA unwinding element binding protein DUE-B interacts with Cdc45 in preinitiation complex formation. Mol Cell Biol 30(6):1495–1507PubMedCentralPubMedGoogle Scholar
  21. Collart C, Allen GE, Bradshaw CR, Smith JC, Zegerman P (2013) Titration of four replication factors is essential for the Xenopus laevis midblastula transition. Science 341(6148):893–896PubMedCentralPubMedGoogle Scholar
  22. Coudreuse D, Nurse P (2010) Driving the cell cycle with a minimal CDK control network. Nature 468(7327):1074–1079PubMedGoogle Scholar
  23. Crevel G, Vo N, Crevel I, Hamid S, Hoa L, Miyata S, Cotterill S (2012) Drosophila RecQ4 is directly involved in both DNA replication and the response to UV damage in S2 cells. PLoS One 7(11):e49505PubMedGoogle Scholar
  24. Croteau DL, Singh DK, Hoh Ferrarelli L, Lu H, Bohr VA (2012) RECQL4 in genomic instability and aging. Trends Genet 28(12):624–631PubMedCentralPubMedGoogle Scholar
  25. Diffley JF (2004) Regulation of early events in chromosome replication. Curr Biol 14(18):R778–R786PubMedGoogle Scholar
  26. Drury LS, Diffley JF (2009) Factors affecting the diversity of DNA replication licensing control in eukaryotes. Curr Biol 19(6):530–535PubMedGoogle Scholar
  27. 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(5):231–240PubMedGoogle Scholar
  28. 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 U S A 106(48):20240–20245PubMedCentralPubMedGoogle Scholar
  29. Fernandez-Cid A, Riera A, Tognetti S, Herrera MC, Samel S, Evrin C, Winkler C, Gardenal E, Uhle S, Speck C (2013) An ORC/Cdc6/MCM2-7 complex is formed in a multistep reaction to serve as a platform for MCM double-hexamer assembly. Mol Cell 50(4):577–588PubMedGoogle Scholar
  30. 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(1):242–248PubMedGoogle Scholar
  31. Fu YV, Yardimci H, Long DT, Ho TV, Guainazzi A, Bermudez VP, Hurwitz J, van Oijen A, Scharer OD, Walter JC (2011) Selective bypass of a lagging strand roadblock by the eukaryotic replicative DNA helicase. Cell 146(6):931–941PubMedCentralPubMedGoogle Scholar
  32. Fukuura M, Nagao K, Obuse C, Takahashi TS, Nakagawa T, Masukata H (2011) CDK promotes interactions of Sld3 and Drc1 with Cut5 for initiation of DNA replication in fission yeast. Mol Biol Cell 22(14):2620–2633PubMedCentralPubMedGoogle Scholar
  33. Gaggioli V, Zeiser E, Rivers D, Bradshaw CR, Ahringer J, Zegerman P (2014) CDK phosphorylation of SLD-2 is required for replication initiation and germline development in C. elegans. J Cell Biol 204(4):507–522PubMedCentralPubMedGoogle Scholar
  34. Ge XQ, Jackson DA, Blow JJ (2007) Dormant origins licensed by excess Mcm2-7 are required for human cells to survive replicative stress. Genes Dev 21(24):3331–3341PubMedCentralPubMedGoogle Scholar
  35. Ghaemmaghami S, Huh WK, Bower K, Howson RW, Belle A, Dephoure N, O’Shea EK, Weissman JS (2003) Global analysis of protein expression in yeast. Nature 425(6959):737–741PubMedGoogle Scholar
  36. Going JJ, Nixon C, Dornan ES, Boner W, Donaldson MM, Morgan IM (2007) Aberrant expression of TopBP1 in breast cancer. Histopathology 50(4):418–424PubMedGoogle Scholar
  37. Grieb BC, Chen X, Eischen CM (2014a) MTBP is overexpressed in triple-negative breast cancer and contributes to its growth and survival. Mol Cancer Res 12(9):1216–1224PubMedGoogle Scholar
  38. Grieb BC, Gramling MW, Arrate MP, Chen X, Beauparlant SL, Haines DS, Xiao H, Eischen CM (2014b) Oncogenic protein MTBP interacts with MYC to promote tumorigenesis. Cancer Res 74(13):3591–3602PubMedCentralPubMedGoogle Scholar
  39. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674PubMedGoogle Scholar
  40. Hashimoto Y, Puddu F, Costanzo V (2012) RAD51- and MRE11-dependent reassembly of uncoupled CMG helicase complex at collapsed replication forks. Nat Struct Mol Biol 19(1):17–24PubMedCentralGoogle Scholar
  41. Heller RC, Kang S, Lam WM, Chen S, Chan CS, Bell SP (2011) Eukaryotic origin-dependent DNA replication in vitro reveals sequential action of DDK and S-CDK kinases. Cell 146(1):80–91PubMedCentralPubMedGoogle Scholar
  42. Hills SA, Diffley JF (2014) DNA replication and oncogene-induced replicative stress. Curr Biol 24(10):R435–R444PubMedGoogle Scholar
  43. Ibarra A, Schwob E, Mendez J (2008) Excess MCM proteins protect human cells from replicative stress by licensing backup origins of replication. Proc Natl Acad Sci U S A 105(26):8956–8961PubMedCentralPubMedGoogle Scholar
  44. Ilves I, Petojevic T, Pesavento JJ, Botchan MR (2010) Activation of the MCM2-7 helicase by association with Cdc45 and GINS proteins. Mol Cell 37(2):247–258PubMedGoogle Scholar
  45. Im JS, Ki SH, Farina A, Jung DS, Hurwitz J, Lee JK (2009) Assembly of the Cdc45-Mcm2-7-GINS complex in human cells requires the Ctf4/And-1, RecQL4, and Mcm10 proteins. Proc Natl Acad Sci U S A 106(37):15628–15632PubMedCentralPubMedGoogle Scholar
  46. Itou H, Muramatsu S, Shirakihara Y, Araki H (2014) Crystal structure of the homology domain of the eukaryotic DNA replication proteins sld3/treslin. Structure 22(9):1341–1347PubMedGoogle Scholar
  47. 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(10):6102–6109PubMedCentralPubMedGoogle Scholar
  48. 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(8):2097–2107PubMedCentralPubMedGoogle Scholar
  49. Karppinen SM, Erkko H, Reini K, Pospiech H, Heikkinen K, Rapakko K, Syvaoja JE, Winqvist R (2006) Identification of a common polymorphism in the TopBP1 gene associated with hereditary susceptibility to breast and ovarian cancer. Eur J Cancer 42(15):2647–2652PubMedGoogle Scholar
  50. Kawabata T, Luebben SW, Yamaguchi S, Ilves I, Matise I, Buske T, Botchan MR, Shima N (2011) Stalled fork rescue via dormant replication origins in unchallenged S phase promotes proper chromosome segregation and tumor suppression. Mol Cell 41(5):543–553PubMedCentralPubMedGoogle Scholar
  51. Kumagai A, Shevchenko A, Dunphy WG (2010) Treslin collaborates with TopBP1 in triggering the initiation of DNA replication. Cell 140(3):349–359PubMedCentralPubMedGoogle Scholar
  52. Kumagai A, Shevchenko A, Dunphy WG (2011) Direct regulation of Treslin by cyclin-dependent kinase is essential for the onset of DNA replication. J Cell Biol 193(6):995–1007PubMedGoogle Scholar
  53. Labib K (2010) How do Cdc7 and cyclin-dependent kinases trigger the initiation of chromosome replication in eukaryotic cells? Genes Dev 24(12):1208–1219PubMedCentralPubMedGoogle Scholar
  54. Lecona E, Fernandez-Capetillo O (2014) Replication stress and cancer: it takes two to tango. Exp Cell Res Google Scholar
  55. Li Y, Araki H (2013) Loading and activation of DNA replicative helicases: the key step of initiation of DNA replication. Genes Cells 18(4):266–277PubMedCentralPubMedGoogle Scholar
  56. Liu Y (2010) Rothmund-Thomson syndrome helicase, RECQ4: on the crossroad between DNA replication and repair. DNA Repair (Amst) 9(3):325–330Google Scholar
  57. Lobner-Olesen A, Skarstad K, Hansen FG, von Meyenburg K, Boye E (1989) The DNAA protein determines the initiation mass of Escherichia coli K-12. Cell 57(5):881–889PubMedGoogle Scholar
  58. Loog M, Morgan DO (2005) Cyclin specificity in the phosphorylation of cyclin-dependent kinase substrates. Nature 434(7029):104–108PubMedGoogle Scholar
  59. Makarova KS, Koonin EV (2013) Archaeology of eukaryotic DNA replication. Cold Spring Harb Perspect Med 3(10):a012963PubMedGoogle Scholar
  60. Malumbres M, Barbacid M (2009) Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 9(3):153–166PubMedGoogle Scholar
  61. Mann MB, Hodges CA, Barnes E, Vogel H, Hassold TJ, Luo G (2005) Defective sister-chromatid cohesion, aneuploidy and cancer predisposition in a mouse model of type II Rothmund-Thomson syndrome. Hum Mol Genet 14(6):813–825PubMedGoogle Scholar
  62. Mantiero D, Mackenzie A, Donaldson A, Zegerman P (2011) Limiting replication initiation factors execute the temporal programme of origin firing in budding yeast. EMBO J 30(23):4805–4814PubMedCentralPubMedGoogle Scholar
  63. 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(6872):651–655PubMedGoogle Scholar
  64. Matsuno K, Kumano M, Kubota Y, Hashimoto Y, Takisawa H (2006) The N-terminal noncatalytic region of Xenopus RecQ4 is required for chromatin binding of DNA polymerase alpha in the initiation of DNA replication. Mol Cell Biol 26(13):4843–4852PubMedCentralPubMedGoogle Scholar
  65. Mechali M (2010) Eukaryotic DNA replication origins: many choices for appropriate answers. Nat Rev Mol Cell Biol 11(10):728–738PubMedGoogle Scholar
  66. Mimura S, Seki T, Tanaka S, Diffley JF (2004) Phosphorylation-dependent binding of mitotic cyclins to Cdc6 contributes to DNA replication control. Nature 431(7012):1118–1123PubMedGoogle Scholar
  67. Morrison HG, McArthur AG, Gillin FD, Aley SB, Adam RD, Olsen GJ, Best AA, Cande WZ, Chen F, Cipriano MJ, Davids BJ, Dawson SC, Elmendorf HG, Hehl AB, Holder ME, Huse SM, Kim UU, Lasek-Nesselquist E, Manning G, Nigam A, Nixon JE, Palm D, Passamaneck NE, Prabhu A, Reich CI, Reiner DS, Samuelson J, Svard SG, Sogin ML (2007) Genomic minimalism in the early diverging intestinal parasite Giardia lamblia. Science 317(5846):1921–1926PubMedGoogle Scholar
  68. Moses AM, Liku ME, Li JJ, Durbin R (2007) Regulatory evolution in proteins by turnover and lineage-specific changes of cyclin-dependent kinase consensus sites. Proc Natl Acad Sci U S A 104(45):17713–17718PubMedCentralPubMedGoogle Scholar
  69. Muramatsu S, Hirai K, Tak YS, Kamimura Y, Araki H (2010) CDK-dependent complex formation between replication proteins Dpb11, Sld2, Pol (epsilon}, and GINS in budding yeast. Genes Dev 24(6):602–612PubMedCentralPubMedGoogle Scholar
  70. 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(5):1462–1472PubMedCentralPubMedGoogle Scholar
  71. Nguyen VQ, Co C, Li JJ (2001) Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms. Nature 411(6841):1068–1073PubMedGoogle Scholar
  72. Ohlenschlager O, Kuhnert A, Schneider A, Haumann S, Bellstedt P, Keller H, Saluz HP, Hortschansky P, Hanel F, Grosse F, Gorlach M, Pospiech H (2012) The N-terminus of the human RecQL4 helicase is a homeodomain-like DNA interaction motif. Nucleic Acids Res 40(17):8309–8324PubMedCentralPubMedGoogle Scholar
  73. On KF, Beuron F, Frith D, Snijders AP, Morris EP, Diffley JF (2014) Prereplicative complexes assembled in vitro support origin-dependent and independent DNA replication. EMBO J 33(6):605–620PubMedCentralPubMedGoogle Scholar
  74. Pagliuca FW, Collins MO, Lichawska A, Zegerman P, Choudhary JS, Pines J (2011) Quantitative proteomics reveals the basis for the biochemical specificity of the cell-cycle machinery. Mol Cell 43(3):406–417PubMedGoogle Scholar
  75. Patel PK, Kommajosyula N, Rosebrock A, Bensimon A, Leatherwood J, Bechhoefer J, Rhind N (2008) The Hsk1(Cdc7) replication kinase regulates origin efficiency. Mol Biol Cell 19(12):5550–5558PubMedCentralPubMedGoogle Scholar
  76. Pir P, Gutteridge A, Wu J, Rash B, Kell DB, Zhang N, Oliver SG (2012) The genetic control of growth rate: a systems biology study in yeast. BMC Syst Biol 6:4PubMedCentralPubMedGoogle Scholar
  77. 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(1):29–39PubMedGoogle Scholar
  78. Remus D, Diffley JF (2009) Eukaryotic DNA replication control: lock and load, then fire. Curr Opin Cell Biol 21(6):771–777PubMedGoogle Scholar
  79. 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(4):719–730PubMedCentralPubMedGoogle Scholar
  80. Rhind N, Gilbert DM (2013) DNA replication timing. Cold Spring Harb Perspect Biol 5(8):a010132PubMedCentralPubMedGoogle Scholar
  81. Sanchez-Pulido L, Diffley JF, Ponting CP (2010) Homology explains the functional similarities of Treslin/Ticrr and Sld3. Curr Biol 20(12):R509–R510PubMedGoogle Scholar
  82. Sangrithi MN, Bernal JA, Madine M, Philpott A, Lee J, Dunphy WG, Venkitaraman AR (2005) Initiation of DNA replication requires the RECQL4 protein mutated in Rothmund-Thomson syndrome. Cell 121(6):887–898PubMedGoogle Scholar
  83. Sansam CL, Cruz NM, Danielian PS, Amsterdam A, Lau ML, Hopkins N, Lees JA (2010) A vertebrate gene, ticrr, is an essential checkpoint and replication regulator. Genes Dev 24(2):183–194PubMedCentralPubMedGoogle Scholar
  84. Sheu YJ, Stillman B (2006) Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression. Mol Cell 24(1):101–113PubMedGoogle Scholar
  85. Sheu YJ, Stillman B (2010) The Dbf4-Cdc7 kinase promotes S phase by alleviating an inhibitory activity in Mcm4. Nature 463(7277):113–117PubMedCentralPubMedGoogle Scholar
  86. Siddiqui K, On KF, Diffley JF (2013) Regulating DNA replication in eukarya. Cold Spring Harb Perspect Biol 5(9)Google Scholar
  87. Skarstad K, Katayama T (2013) Regulating DNA replication in bacteria. Cold Spring Harb Perspect Biol 5(4):a012922PubMedCentralPubMedGoogle Scholar
  88. Sun J, Fernandez-Cid A, Riera A, Tognetti S, Yuan Z, Stillman B, Speck C, Li H (2014) Structural and mechanistic insights into Mcm2-7 double-hexamer assembly and function. Genes Dev 28(20):2291–2303PubMedCentralPubMedGoogle Scholar
  89. Tak YS, Tanaka Y, Endo S, Kamimura Y, Araki H (2006) A CDK-catalysed regulatory phosphorylation for formation of the DNA replication complex Sld2-Dpb11. EMBO J 25(9):1987–1996PubMedCentralPubMedGoogle Scholar
  90. Tanaka S, Araki H (2011) Multiple regulatory mechanisms to inhibit untimely initiation of DNA replication are important for stable genome maintenance. PLoS Genet 7(6):e1002136PubMedCentralPubMedGoogle Scholar
  91. Tanaka S, Umemori T, Hirai K, Muramatsu S, Kamimura Y, Araki H (2007) CDK-dependent phosphorylation of Sld2 and Sld3 initiates DNA replication in budding yeast. Nature 445(7125):328–332PubMedGoogle Scholar
  92. Tanaka S, Nakato R, Katou Y, Shirahige K, Araki H (2011) Origin association of Sld3, Sld7, and Cdc45 proteins is a key step for determination of origin-firing timing. Curr Biol 21(24):2055–2063PubMedGoogle Scholar
  93. Tanaka S, Komeda Y, Umemori T, Kubota Y, Takisawa H, Araki H (2013) Efficient initiation of DNA replication in eukaryotes requires Dpb11/TopBP1-GINS interaction. Mol Cell Biol 33(13):2614–2622PubMedCentralPubMedGoogle Scholar
  94. Thangavel S, Mendoza-Maldonado R, Tissino E, Sidorova JM, Yin J, Wang W, Monnat RJ Jr, Falaschi A, Vindigni A (2010) Human RECQ1 and RECQ4 helicases play distinct roles in DNA replication initiation. Mol Cell Biol 30(6):1382–1396PubMedCentralPubMedGoogle Scholar
  95. Ubersax JA, Woodbury EL, Quang PN, Paraz M, Blethrow JD, Shah K, Shokat KM, Morgan DO (2003) Targets of the cyclin-dependent kinase Cdk1. Nature 425(6960):859–864PubMedGoogle Scholar
  96. Wardlaw CP, Carr AM, Oliver AW (2014) TopBP1: a BRCT-scaffold protein functioning in multiple cellular pathways. DNA Repair (Amst) 22:165–174Google Scholar
  97. 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(19):5334–5346PubMedCentralPubMedGoogle Scholar
  98. Weinreich M, Palacios DeBeer MA, Fox CA (2004) The activities of eukaryotic replication origins in chromatin. Biochim Biophys Acta 1677(1–3):142–157PubMedGoogle Scholar
  99. Wong PG, Winter SL, Zaika E, Cao TV, Oguz U, Koomen JM, Hamlin JL, Alexandrow MG (2011) Cdc45 limits replicon usage from a low density of preRCs in mammalian cells. PLoS One 6(3):e17533PubMedCentralPubMedGoogle Scholar
  100. Woodward AM, Gohler T, Luciani MG, Oehlmann M, Ge X, Gartner A, Jackson DA, Blow JJ (2006) Excess Mcm2-7 license dormant origins of replication that can be used under conditions of replicative stress. J Cell Biol 173(5):673–683PubMedCentralPubMedGoogle Scholar
  101. Wu PY, Nurse P (2009) Establishing the program of origin firing during S phase in fission yeast. Cell 136(5):852–864. doi: 10.1016/j.cell.2009.01.017
  102. Wu J, Capp C, Feng L, Hsieh TS (2008) Drosophila homologue of the Rothmund-Thomson syndrome gene: essential function in DNA replication during development. Dev Biol 323(1):130–142PubMedGoogle Scholar
  103. Xu X, Rochette PJ, Feyissa EA, Su TV, Liu Y (2009a) MCM10 mediates RECQ4 association with MCM2-7 helicase complex during DNA replication. EMBO J 28(19):3005–3014PubMedCentralPubMedGoogle Scholar
  104. Xu Y, Lei Z, Huang H, Dui W, Liang X, Ma J, Jiao R (2009b) dRecQ4 is required for DNA synthesis and essential for cell proliferation in Drosophila. PLoS One 4(7):e6107PubMedCentralPubMedGoogle Scholar
  105. Yabuuchi H, Yamada Y, Uchida T, Sunathvanichkul T, Nakagawa T, Masukata H (2006) Ordered assembly of Sld3, GINS and Cdc45 is distinctly regulated by DDK and CDK for activation of replication origins. EMBO J 25(19):4663–4674PubMedCentralPubMedGoogle Scholar
  106. Yoshida K, Poveda A, Pasero P (2013) Time to be versatile: regulation of the replication timing program in budding yeast. J Mol Biol 425(23):4696–4705PubMedGoogle Scholar
  107. Zegerman P, Diffley JF (2007) Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast. Nature 445(7125):281–285PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of Biochemistry, Wellcome Trust/Cancer Research UK Gurdon InstituteUniversity of CambridgeCambridgeUK

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