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Role of DDK in Replication Initiation

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The Initiation of DNA Replication in Eukaryotes

Abstract

DDK (Dbf4-dependent kinase) is a serine/threonine protein kinase conserved from yeast to humans. DDK is composed of two subunits, Cdc7 protein kinase and Dbf4 regulatory subunits in 1:1 stoichiometry. Both the CDC7 and DBF4 genes were discovered in budding yeast from the analysis of conditional mutants that were defective in the initiation of DNA replication. Cdc7 and Dbf4 homologues have been identified in many eukaryotes and are important in DNA replication, indicating the role of DDK was also conserved. This knowledge has been translated medically as oncogenic DDK overexpression is currently a target of therapeutic inhibitors. DDK activity is cell cycle regulated because it is inactive in G1 phase cells due to the absence of the essential Dbf4 protein as a result of APC-dependent proteolysis. It is clear from both genetic and biochemical studies that several subunits of the hexameric MCM2–7 DNA helicase/ATPase are substrates of DDK. In an allosteric model of DDK function, DDK phosphorylates the Mcm4 protein in the misaligned MCM2–7 double hexamer bound to origins of replication to align the important catalytic residues of the enzyme and to load other proteins to form a CMG (Cdc45-MCM-GINS) holoenzyme. To complete the initiation reaction, the loading of several other replication proteins is also needed, which requires ensuing CDK (cyclin-dependent kinase) phosphorylation. DDK has other substrates important for mutagenesis by TLS (translesion synthesis), meiotic recombination, and chromosome cohesion. Because all these processes are chromatin-based, DDK may have evolved to regulate chromatin-bound proteins in DNA metabolism.

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References

  1. Hartwell LH. Genetic control of the cell division cycle in yeast II. Genes controlling DNA replication and its initiation. J Mol Biol. 1971;59:183–94.

    Article  CAS  PubMed  Google Scholar 

  2. Hartwell LH. Three additional genes required for deoxyribonucleic acid synthesis in Saccharomyces cerevisiae. J Bacteriol. 1973;115:966–74.

    PubMed Central  CAS  PubMed  Google Scholar 

  3. Hollingsworth RE Jr. Molecular Biology of the CDC7 gene and protein of Saccharomyces cerevisiae [PhD]. University of Colorado; 1990.

    Google Scholar 

  4. Johnston LH, Thomas AP. The isolation of new DNA synthesis mutants in the yeast Saccharomyces cerevisiae. Mol Gen Genet. 1982;186(3):439–44.

    Article  CAS  PubMed  Google Scholar 

  5. Johnston LH, Thomas AP. A further two mutants defective in initiation of the S phase in the yeast Saccharomyces cerevisiae. Mol Gen Genet. 1982;186:445–8.

    Article  CAS  PubMed  Google Scholar 

  6. Kitada K, Johnston LH, editors. The Saccharomyces cerevisiae DBF4 gene, required for the G1Æ S phase transition, suppresses temperature-sensitive cdc7 mutations. 1991 Yeast Genetics and Molecular Biology Meeting; 1991; San Francisco, CA: Genetics Society of America.

    Google Scholar 

  7. Patterson M, Sclafani RA, Fangman WL, Rosamond J. Molecular characterization of cell cycle gene CDC7 from Saccharomyces cerevisiae. Mol Cell Biol. 1986;6:1590–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Chapman JW, Johnston LH. The yeast gene, DBF4, essential for entry into the S phase is cell cycle regulated. Exp Cell Res. 1989;180:419–28.

    Article  CAS  PubMed  Google Scholar 

  9. Hollingsworth Jr RE, Sclafani RA. DNA metabolism gene CDC7 from yeast encodes a serine (threonine) protein kinase. Proc Natl Acad Sci U S A. 1990;87:6272–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Yoon H-J, Campbell JL. The CDC7 protein of Saccharomyces cerevisiae is a phosphoprotein that contains protein kinase activity. Proc Natl Acad Sci U S A. 1991;88:3574–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Masai H, Miyake T, Arai K-I. hsk1 +, a Schizosaccharomyces pombe gene related to Saccharomyces cerevisiae CDC7, is required for chromosomal replication. EMBO J. 1995;14(13):3094–104.

    PubMed Central  CAS  PubMed  Google Scholar 

  12. Masai H, Arai K. Cdc7 kinase complex: a key regulator in the initiation of DNA replication. J Cell Physiol. 2002;190(3):287–96.

    Article  CAS  PubMed  Google Scholar 

  13. Matsumoto S, Hayano M, Kanoh Y, Masai H. Multiple pathways can bypass the essential role of fission yeast Hsk1 kinase in DNA replication initiation. J Cell Biol. 2011;195(3):387–401.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Sato N, Arai K-I, Masai H. Human and Xenopus cDNAs encoding budding yeast Cdc7-related kinases: in vitro phosphorylation of MCM subunits by a putative human homolgue of Cdc7. EMBO J. 1997;16:4340–51.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Hess GF, Drong RF, Weiland KL, Sligthom JL, Sclafani RA, Hollingsworth Jr RE. A human homolog of the yeast CDC7 gene is overexpressed in some tumors and transformed cell lines. Gene. 1998;211:133–40.

    Article  CAS  PubMed  Google Scholar 

  16. Faul T, Staib C, Nanda I, Schmid M, Grummt F. Identification and characterization of mouse homologue to yeast Cdc7 protein and chromosomal localization of the cognate mouse gene Cdc7l. Chromosoma. 1999;108(1):26–31.

    Article  CAS  PubMed  Google Scholar 

  17. Brown GW, Kelly TJ. Purification of Hsk1, a minichromosome maintenance protein kinase from fission yeast. J Biol Chem. 1998;273(34):22083–90.

    Article  CAS  PubMed  Google Scholar 

  18. Jares P, Luciani MG, Blow JJ. A Xenopus Dbf4 homolog is required for Cdc7 chromatin binding and DNA replication. BMC Mol Biol. 2004;5:5.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Lepke M, Putter V, Staib C, Kneissl M, Berger C, Hoehn K, et al. Identification, characterization and chromosomal localization of the cognate human and murine DBF4 genes. Mol Gen Genet. 1999;262(2):220–9.

    Article  CAS  PubMed  Google Scholar 

  20. Jackson AL, Pahl PMB, Harrison K, Rosamond J, Sclafani RA. Cell cycle regulation of the yeast Cdc7 protein kinase by association with the Dbf4 protein. Mol Cell Biol. 1993;13(5):2899–908.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Dowell SJ, Romanowski P, Diffley JFX. Interaction of Dbf4, the Cdc7 protein kinase regulatory subunit, with yeast regulatory origins in vivo. Science. 1994;265:1243–6.

    Article  CAS  PubMed  Google Scholar 

  22. Harkins V, Gabrielse C, Haste L, Weinreich M. Budding yeast Dbf4 sequences required for Cdc7 kinase activation and identification of a functional relationship between the Dbf4 and Rev1 BRCT domains. Genetics. 2009;183(4):1269–82.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Roberts BT, Ying CY, Gautier J, Maller JL. DNA replication in vertebrates requires a homolog of the Cdc7 protein kinase. Proc Natl Acad Sci U S A. 1999;96(6):2800–4.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Davey MJ, Andrighetti HJ, Ma X, Brandl CJ. A synthetic human kinase can control cell cycle progression in budding yeast. G3 (Bethesda). 2011;1(4):317–25.

    Article  CAS  Google Scholar 

  25. Weinreich M, Stillman B. Cdc7p-Dbf4p kinase binds to chromatin during S phase and is regulated by both the APC and the RAD53 checkpoint pathway. EMBO J. 1999;18(19):5334–46.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Cheng L, Collyer T, Hardy CF. Cell cycle regulation of DNA replication initiator factor Dbf4p. Mol Cell Biol. 1999;19(6):4270–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Ferreira MF, Santocanale C, Drury LS, Diffley JF. Dbf4p, an essential S phase-promoting factor, is targeted for degradation by the anaphase-promoting complex. Mol Cell Biol. 2000;20(1):242–8.

    Article  CAS  PubMed  Google Scholar 

  28. Morgan DO (2007) The Cell Cycle. Primers In Biology. New Science Press Ltd., London UK.

    Google Scholar 

  29. Oshiro G, Owens JC, Shellman Y, Sclafani RA, Li JJ. Cell cycle control of cdc7p kinase activity through regulation of dbf4p stability. Mol Cell Biol. 1999;19(7):4888–96.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Takeda T, Ogino K, Matsui E, Cho MK, Kumagai H, Miyake T, et al. 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. 1999;19(8):5535–47.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Jiang W, Hunter T. Identification and characterization of a human protein kinase related to budding yeast Cdc7p. Proc Natl Acad Sci U S A. 1997;94:14320–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Furukohri A, Sato N, Masai H, Arai K, Sugino A, Waga S. Identification and characterization of a Xenopus homolog of Dbf4, a regulatory subunit of the Cdc7 protein kinase required for the initiation of DNA replication. J Biochem. 2003;134(3):447–57.

    Article  CAS  PubMed  Google Scholar 

  33. Montagnoli A, Bosotti R, Villa F, Rialland M, Brotherton D, Mercurio C, et al. Drf1, a novel regulatory subunit for human Cdc7 kinase. EMBO J. 2002;21(12):3171–81.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Takahashi TS, Walter JC. Cdc7-Drf1 is a developmentally regulated protein kinase required for the initiation of vertebrate DNA replication. Genes Dev. 2005;19(19):2295–300.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Yoshizawa-Sugata N, Ishii A, Taniyama C, Matsui E, Arai K, Masai H. A second human Dbf4/ASK-related protein, Drf1/ASKL1, is required for efficient progression of S and M phases. J Biol Chem. 2005;280(13):13062–70.

    Article  CAS  PubMed  Google Scholar 

  36. Mantiero D, Mackenzie A, Donaldson A, Zegerman P. Limiting replication initiation factors execute the temporal programme of origin firing in budding yeast. EMBO J. 2011;30(23):4805–14.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Hughes S, Elustondo F, Di Fonzo A, Leroux FG, Wong AC, Snijders AP, et al. Crystal structure of human CDC7 kinase in complex with its activator DBF4. Nat Struct Mol Biol. 2012;19(11):1101–7.

    Article  CAS  PubMed  Google Scholar 

  38. Shellman YG, Schauer IE, Oshiro G, Dohrmann P, Sclafani RA. Oligomers of yeast Cdc7/Dbf4 protein kinase exist in the cell. Mol Gen Genet. 1998;259:429–36.

    Article  CAS  PubMed  Google Scholar 

  39. Kaplan DL, Bruck I. Methods to study kinase regulation of the replication fork helicase. Methods. 2010;51:358–62.

    Article  CAS  PubMed  Google Scholar 

  40. Bousset K, Diffley JFX. The Cdc7 protein kinase is required for origin firing during S phase. Genes Dev. 1998;12:480–90.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Donaldson AD, Fangman WF, Brewer BJ. Cdc7 is required throughout the yeast S phase to activate replication origins. Genes Dev. 1998;491:491–501.

    Article  Google Scholar 

  42. Natsume T, Muller CA, Katou Y, Retkute R, Gierlinski M, Araki H, et al. Kinetochores coordinate pericentromeric cohesion and early DNA replication by cdc7-dbf4 kinase recruitment. Mol Cell. 2013;50(5):661–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Hardy CFJ, Dryga O, Seematter S, Pahl PMB, Sclafani RA. mcm5/cdc46-bob1 bypasses the requirement for the S phase activator Cdc7p. Proc Natl Acad Sci U S A. 1997;94:3151–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Sclafani RA, Holzen TM. Cell cycle regulation of DNA replication. Annu Rev Genet. 2007;41:237–80.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Tye B-K. MCM proteins in DNA replication. Annu Rev Biochem. 1999;68:649–86.

    Article  CAS  PubMed  Google Scholar 

  46. Todorov IT, Attaran A, Kearsey SE. BM28, a human member of the MCM2-3-5 family, is displaced from chromatin during DNA replication. J Cell Biol. 1995;129:1433–45.

    Article  CAS  PubMed  Google Scholar 

  47. Young MR, Tye BK. Mcm2 and Mcm3 are constitutive nuclear proteins that exhibit distinct isoforms and bind chromatin during specific cell cycle stages of Saccharomyces cerevisiae. Mol Biol Cell. 1997;8:1587–601.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Lei M, Kawasaki Y, Young MR, Kihara M, Sugino A, Tye BK. Mcm2 is a target of regulation by Cdc7-Dbf4 during the initiation of DNA synthesis. Genes Dev. 1997;11:3365–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Bruck I, Kaplan D. Dbf4-Cdc7 phosphorylation of Mcm2 is required for cell growth. J Biol Chem. 2009;284(42):28823–31.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Bruck I, Kaplan DL. The Dbf4-Cdc7 kinase promotes Mcm2-7 ring opening to allow for single-stranded DNA extrusion and helicase assembly. J Biol Chem. 2015;290:1210–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Cho WH, Lee YJ, Kong SI, Hurwitz J, Lee JK. CDC7 kinase phosphorylates serine residues adjacent to acidic amino acids in the minichromosome maintenance 2 protein. Proc Natl Acad Sci U S A. 2006;103(31):11521–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Meggio F, Pinna LA. One-thousand-and-one substrates of protein kinase CK2? FASEB J. 2003;17(3):349–68.

    Article  CAS  PubMed  Google Scholar 

  53. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. The protein kinase complement of the human genome. Science. 2002;298(5600):1912–34.

    Article  CAS  PubMed  Google Scholar 

  54. Montagnoli A, Valsasina B, Brotherton D, Troiani S, Rainoldi S, Tenca P, et al. Identification of Mcm2 phosphorylation sites by S-phase-regulating kinases. J Biol Chem. 2006;281(15):10281–90.

    Article  CAS  PubMed  Google Scholar 

  55. Wan L, Niu H, Futcher B, Zhang C, Shokat KM, Boulton SJ, et al. Cdc28-Clb5 (CDK-S) and Cdc7-Dbf4 (DDK) collaborate to initiate meiotic recombination in yeast. Genes Dev. 2008;22(3):386–97.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Sheu YJ, Stillman B. Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression. Mol Cell. 2006;24(1):101–13.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. Sheu Y-J, Stillman B. The Dbf4-Cdc7 kinase promotes S phase by alleviating an inhibitory activity in Mcm4. Nature. 2010;463(7277):113–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Tanaka S, Umemori T, Hirai K, Muramatsu S, Kamimura Y, Araki H. CDK-dependent phosphorylation of Sld2 and Sld3 initiates DNA replication in budding yeast. Nature. 2007;445(7125):328–32.

    Article  CAS  PubMed  Google Scholar 

  59. Zegerman P, Diffley JF. Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast. Nature. 2007;445(7125):281–5.

    Article  CAS  PubMed  Google Scholar 

  60. Masai H, Taniyama C, Ogino K, Matsui E, Kakusho N, Matsumoto S, et al. Phosphorylation of MCM4 by Cdc7 kinase facilitates its interaction with Cdc45 on the chromatin. J Biol Chem. 2006;281(51):39249–61.

    Article  CAS  PubMed  Google Scholar 

  61. Randell JC, Fan A, Chan C, Francis LI, Heller RC, Galani K, et al. Mec1 Is one of multiple kinases that prime the Mcm2-7 helicase for phosphorylation by Cdc7. Mol Cell. 2010;40(3):353–63.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Jiang W, McDonald D, Hope TJ, Hunter T. Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of DNA replication. EMBO J. 1999;18(20):5703–13.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Nougarede R, Della Seta F, Zarzov P, Schwob E. Hierarchy of S-phase-promoting factors: yeast Dbf4-cdc7 kinase requires prior S-phase cyclin-dependent kinase activation. Mol Cell Biol. 2000;20(11):3795–806.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  64. Walter JC. Evidence for sequential action of cdc7 and cdk2 protein kinases during initiation of DNA replication in Xenopus egg extracts. J Biol Chem. 2000;275(50):39773–8.

    Article  CAS  PubMed  Google Scholar 

  65. Heller RC, Kang S, Lam WM, Chen S, Chan CS, Bell SP. Eukaryotic origin-dependent DNA replication in vitro reveals sequential action of DDK and S-CDK kinases. Cell. 2011;146(1):80–91.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. Geraghty DS, Ding M, Heintz NH, Pederson DS. Premature structural changes at replication origins in a yeast minichromosome maintenance (MCM) mutant. J Biol Chem. 2000;275(24):18011–21.

    Article  CAS  PubMed  Google Scholar 

  67. Hollingsworth RE, Ostroff RM, Klein MB, Niswander LA, Sclafani RA. Molecular genetic studies of the Cdc7 protein kinase and induced mutagenesis in yeast. Genetics. 1992;132:53–62.

    CAS  PubMed  Google Scholar 

  68. Sclafani RA, Patterson M, Rosamond J, Fangman WL. Differential regulation of the yeast CDC7 gene during mitosis and meiosis. Mol Cell Biol. 1988;8(1):293–300.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Pessoa-Brandão L. Genetic and molecular studies of Saccahromyces cerevisiae Cdc7-Dbf4 kinase function in DNA damage-induced mutagenesis [Dissertation/Thesis]. Aurora, Colorado: University of Colorado Health Sciences Center; 2005.

    Google Scholar 

  70. Cheng AN, Jiang SS, Fan CC, Lo YK, Kuo CY, Chen CH, et al. Increased Cdc7 expression is a marker of oral squamous cell carcinoma and overexpression of Cdc7 contributes to the resistance to DNA-damaging agents. Cancer Lett. 2013;337(2):218–25.

    Article  CAS  PubMed  Google Scholar 

  71. Choschzick M, Lebeau A, Marx AH, Tharun L, Terracciano L, Heilenkotter U, et al. Overexpression of cell division cycle 7 homolog is associated with gene amplification frequency in breast cancer. Hum Pathol. 2010;41(3):358–65.

    Article  CAS  PubMed  Google Scholar 

  72. Bonte D, Lindvall C, Liu H, Dykema K, Furge K, Weinreich M. Cdc7-Dbf4 kinase overexpression in multiple cancers and tumor cell lines is correlated with p53 inactivation. Neoplasia. 2008;10(9):920–31.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  73. Montagnoli A, Moll J, Colotta F. Targeting cell division cycle 7 kinase: a new approach for cancer therapy. Clin Cancer Res. 2010;16(18):4503–8.

    Article  CAS  PubMed  Google Scholar 

  74. Vanotti E, Amici R, Bargiotti A, Berthelsen J, Bosotti R, Ciavolella A, et al. Cdc7 kinase inhibitors: pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships. J Med Chem. 2008;51(3):487–501.

    Article  CAS  PubMed  Google Scholar 

  75. Montagnoli A, Valsasina B, Croci V, Menichincheri M, Rainoldi S, Marchesi V, et al. A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity. Nat Chem Biol. 2008;4(6):357–65.

    Article  CAS  PubMed  Google Scholar 

  76. Sasi NK, Tiwari K, Soon FF, Bonte D, Wang T, Melcher K, et al. The potent Cdc7-Dbf4 (DDK) kinase inhibitor XL413 has limited activity in many cancer cell lines and discovery of potential new DDK inhibitor scaffolds. PLoS One. 2014;9(11):e113300.

    Article  PubMed Central  PubMed  Google Scholar 

  77. Hoang ML, Leon RP, Pessoa-Brandao L, Hunt S, Raghuraman MK, Fangman WL, et al. Structural changes in Mcm5 protein bypass Cdc7-Dbf4 function and reduce replication origin efficiency in Saccharomyces cerevisiae. Mol Cell Biol. 2007;27(21):7594–602.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  78. Fletcher RJ, Bishop BE, Leon RP, Sclafani RA, Ogata CM, Chen XS. The structure and function of MCM from archaeal M. Thermoautotrophicum. Nat Struct Biol. 2003;10(3):160–7.

    Article  CAS  PubMed  Google Scholar 

  79. Fletcher RJ, Chen XS. Biochemical activities of the BOB1 mutant in Methanobacterium thermoautotrophicum MCM. Biochemistry. 2006;45(2):462–7.

    Article  CAS  PubMed  Google Scholar 

  80. Miller JM, Arachea BT, Epling LB, Enemark EJ. Analysis of the crystal structure of an active MCM hexamer. Elife. 2014;3:e03433.

    PubMed  Google Scholar 

  81. Brandao LN, Ferguson R, Santoro I, Jinks-Robertson S, Sclafani RA. The role of Dbf4-dependent protein kinase in DNA polymerase zeta-dependent mutagenesis in Saccharomyces cerevisiae. Genetics. 2014;197:1111–22.

    Article  PubMed Central  PubMed  Google Scholar 

  82. Pessoa-Brandao L, Sclafani RA. CDC7/DBF4 functions in the translesion synthesis branch of the RAD6 epistasis group in Saccharomyces cerevisiae. Genetics. 2004;167(4):1597–610.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  83. Sasanuma H, Hirota K, Fukuda T, Kakusho N, Kugou K, Kawasaki Y, et al. Cdc7-dependent phosphorylation of Mer2 facilitates initiation of yeast meiotic recombination. Genes Dev. 2008;22(3):398–410.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  84. Sun J, Fernandez-Cid A, Riera A, Tognetti S, Yuan Z, Stillman B, et al. Structural and mechanistic insights into Mcm2-7 double-hexamer assembly and function. Genes Dev. 2014;28(20):2291–303.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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  1. Biochemistry and Molecular Genetics, University of Colorado School of Medicine, MS8101, Aurora, CO, 80045, USA

    Daniel Rossbach & Robert A. Sclafani

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  1. Florida State Univ. College of Medi, TALLAHASSEE, Florida, USA

    Daniel L. Kaplan

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Rossbach, D., Sclafani, R.A. (2016). Role of DDK in Replication Initiation. In: Kaplan, D. (eds) The Initiation of DNA Replication in Eukaryotes. Springer, Cham. https://doi.org/10.1007/978-3-319-24696-3_14

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