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The Role of Mcm10 in Replication Initiation

  • Ryan M. Baxley
  • Yee Mon Thu
  • Anja-Katrin Bielinsky
Chapter

Abstract

Minichromosome maintenance protein 10 (Mcm10) is a conserved component of the eukaryotic DNA replication machinery. Mcm10 promotes the initiation of replication by facilitating DNA unwinding and origin firing. Although the molecular details of this action remain unclear, current data support a scaffolding role for Mcm10 via interactions with DNA and other protein partners. Mcm10 binds both single- and double-stranded DNA, as well as components of the CMG helicase complex, DNA polymerase-α, and Ctf4. Upon initiation, Mcm10 becomes part of the replisome, primarily mediating the initiation of Okazaki fragment synthesis, which involves DNA polymerase-α/primase and the replication clamp PCNA. Mcm10 likely contributes to the recruitment of both of these factors. Emerging concepts predict that steady-state levels of Mcm10 are tightly controlled to balance origin firing and fork progression. Investigations into the cellular requirements for Mcm10 have also revealed a key role in maintaining genome stability. Accordingly, it is not surprising that genetic alterations of MCM10 are associated with cancer. Loss of Mcm10 function is a possible source of DNA damage, whereas overexpression of Mcm10 might serve to facilitate rapid DNA synthesis and proliferation. In this chapter, we provide a comprehensive review of the current literature describing Mcm10’s role in replication initiation. Additionally, we consider how contributions to elongation and other potential functions may affect chromosomal integrity.

Keywords

Mcm10 DNA replication Origin activation Genome stability Replication initiation Replication elongation CMG helicase 

Notes

Acknowledgements

The authors wish to acknowledge funding from the National Institutes of Health R01 GM074917 to A.K.B. R.M.B. was supported by Cancer Biology Training Grant NIH T32 CA009138.

References

  1. 1.
    Dumas LB, Lussky JP, McFarland EJ, Shampay J. New temperature-sensitive mutants of Saccharomyces cerevisiae affecting DNA replication. Mol Gen Genet. 1982;187(1):42–6.PubMedCrossRefGoogle Scholar
  2. 2.
    Solomon NA, Wright MB, Chang S, Buckley AM, Dumas LB, Gaber RF. Genetic and molecular analysis of DNA43 and DNA52: two new cell-cycle genes in Saccharomyces cerevisiae. Yeast. 1992;8(4):273–89.PubMedCrossRefGoogle Scholar
  3. 3.
    Maine GT, Sinha P, Tye BK. Mutants of S. cerevisiae defective in the maintenance of minichromosomes. Genetics. 1984;106(3):365–85.PubMedCentralPubMedGoogle Scholar
  4. 4.
    Merchant AM, Kawasaki Y, Chen Y, Lei M, Tye BK. A lesion in the DNA replication initiation factor Mcm10 induces pausing of elongation forks through chromosomal replication origins in Saccharomyces cerevisiae. Mol Cell Biol. 1997;17(6):3261–71.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Aves SJ, Tongue N, Foster AJ, Hart EA. The essential Schizosaccharomyces pombe cdc23 DNA replication gene shares structural and functional homology with the Saccharomyces cerevisiae DNA43 (MCM10) gene. Curr Genet. 1998;34(3):164–71.PubMedCrossRefGoogle Scholar
  6. 6.
    Christensen TW, Tye BK. Drosophila MCM10 interacts with members of the prereplication complex and is required for proper chromosome condensation. Mol Biol Cell. 2003;14(6):2206–15.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Izumi M, Yanagi K, Mizuno T, Yokoi M, Kawasaki Y, Moon KY, et al. The human homolog of Saccharomyces cerevisiae Mcm10 interacts with replication factors and dissociates from nuclease-resistant nuclear structures in G(2) phase. Nucleic Acids Res. 2000;28(23):4769–77.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Lim HJ, Jeon Y, Jeon CH, Kim JH, Lee H. Targeted disruption of Mcm10 causes defective embryonic cell proliferation and early embryo lethality. Biochim Biophys Acta. 2011;1813(10):1777–83.PubMedCrossRefGoogle Scholar
  9. 9.
    Wohlschlegel JA, Dhar SK, Prokhorova TA, Dutta A, Walter JC. Xenopus Mcm10 binds to origins of DNA replication after Mcm2-7 and stimulates origin binding of Cdc45. Mol Cell. 2002;9(2):233–40.PubMedCrossRefGoogle Scholar
  10. 10.
    Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al. UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem. 2004;25(13):1605–12.PubMedCrossRefGoogle Scholar
  11. 11.
    Du W, Josephrajan A, Adhikary S, Bowles T, Bielinsky AK, Eichman BF. Mcm10 self-association is mediated by an N-terminal coiled-coil domain. PLoS One. 2013;8(7):e70518.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Du W, Stauffer ME, Eichman BF. Structural biology of replication initiation factor Mcm10. Subcell Biochem. 2012;62:197–216.PubMedCrossRefGoogle Scholar
  13. 13.
    Robertson PD, Warren EM, Zhang H, Friedman DB, Lary JW, Cole JL, et al. Domain architecture and biochemical characterization of vertebrate Mcm10. J Biol Chem. 2008;283(6):3338–48.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Fatoba ST, Tognetti S, Berto M, Leo E, Mulvey CM, Godovac-Zimmermann J, et al. Human SIRT1 regulates DNA binding and stability of the Mcm10 DNA replication factor via deacetylation. Nucleic Acids Res. 2013;41(7):4065–79.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Fien K, Cho YS, Lee JK, Raychaudhuri S, Tappin I, Hurwitz J. Primer utilization by DNA polymerase alpha-primase is influenced by its interaction with Mcm10p. J Biol Chem. 2004;279(16):16144–53.PubMedCrossRefGoogle Scholar
  16. 16.
    Ricke RM, Bielinsky AK. Mcm10 regulates the stability and chromatin association of DNA polymerase-alpha. Mol Cell. 2004;16(2):173–85.PubMedCrossRefGoogle Scholar
  17. 17.
    Ricke RM, Bielinsky AK. A conserved Hsp10-like domain in Mcm10 is required to stabilize the catalytic subunit of DNA polymerase-alpha in budding yeast. J Biol Chem. 2006;281(27):18414–25.PubMedCrossRefGoogle Scholar
  18. 18.
    Thu YM, Bielinsky AK. Enigmatic roles of Mcm10 in DNA replication. Trends Biochem Sci. 2013;38(4):184–94.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Warren EM, Huang H, Fanning E, Chazin WJ, Eichman BF. Physical interactions between Mcm10, DNA, and DNA polymerase alpha. J Biol Chem. 2009;284(36):24662–72.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Cook CR, Kung G, Peterson FC, Volkman BF, Lei M. A novel zinc finger is required for Mcm10 homocomplex assembly. J Biol Chem. 2003;278(38):36051–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Okorokov AL, Waugh A, Hodgkinson J, Murthy A, Hong HK, Leo E, et al. Hexameric ring structure of human MCM10 DNA replication factor. EMBO Rep. 2007;8(10):925–30.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Warren EM, Vaithiyalingam S, Haworth J, Greer B, Bielinsky AK, Chazin WJ, et al. Structural basis for DNA binding by replication initiator Mcm10. Structure. 2008;16(12):1892–901.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Di Perna R, Aria V, De Falco M, Sannino V, Okorokov AL, Pisani FM, et al. The physical interaction of Mcm10 with Cdc45 modulates their DNA-binding properties. Biochem J. 2013;454(2):333–43.PubMedCrossRefGoogle Scholar
  24. 24.
    Robertson PD, Chagot B, Chazin WJ, Eichman BF. Solution NMR structure of the C-terminal DNA binding domain of Mcm10 reveals a conserved MCM motif. J Biol Chem. 2010;285(30):22942–9.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Eisenberg S, Korza G, Carson J, Liachko I, Tye BK. Novel DNA binding properties of the Mcm10 protein from Saccharomyces cerevisiae. J Biol Chem. 2009;284(37):25412–20.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Alver RC, Zhang T, Josephrajan A, Fultz BL, Hendrix CJ, Das-Bradoo S, et al. The N-terminus of Mcm10 is important for interaction with the 9-1-1 clamp and in resistance to DNA damage. Nucleic Acids Res. 2014;42(13):8389–404.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Das-Bradoo S, Ricke RM, Bielinsky AK. Interaction between PCNA and diubiquitinated Mcm10 is essential for cell growth in budding yeast. Mol Cell Biol. 2006;26(13):4806–17.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Dua R, Levy DL, Li CM, Snow PM, Campbell JL. In vivo reconstitution of Saccharomyces cerevisiae DNA polymerase epsilon in insect cells. Purification and characterization. J Biol Chem. 2002;277(10):7889–96.PubMedCrossRefGoogle Scholar
  29. 29.
    Schmidt KH, Derry KL, Kolodner RD. Saccharomyces cerevisiae RRM3, a 5′ to 3′ DNA helicase, physically interacts with proliferating cell nuclear antigen. J Biol Chem. 2002;277(47):45331–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Vivona JB, Kelman Z. The diverse spectrum of sliding clamp interacting proteins. FEBS Lett. 2003;546(2–3):167–72.PubMedCrossRefGoogle Scholar
  31. 31.
    Evrin C, Clarke P, Zech J, Lurz R, Sun J, Uhle S, et al. A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication. Proc Natl Acad Sci U S A. 2009;106(48):20240–5.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Masai H, Matsumoto S, You Z, Yoshizawa-Sugata N, Oda M. Eukaryotic chromosome DNA replication: where, when, and how? Annu Rev Biochem. 2010;79:89–130.PubMedCrossRefGoogle Scholar
  33. 33.
    Remus D, Beuron F, Tolun G, Griffith JD, Morris EP, Diffley JF. Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing. Cell. 2009;139(4):719–30.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Bleichert F, Botchan MR, Berger JM. Crystal structure of the eukaryotic origin recognition complex. Nature. 2015;519(7543):321–6.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Ticau S, Friedman LJ, Ivica NA, Gelles J, Bell SP. Single-molecule studies of origin licensing reveal mechanisms ensuring bidirectional helicase loading. Cell. 2015;161(3):513–25.PubMedCrossRefGoogle Scholar
  36. 36.
    Ilves I, Petojevic T, Pesavento JJ, Botchan MR. Activation of the MCM2-7 helicase by association with Cdc45 and GINS proteins. Mol Cell. 2010;37(2):247–58.PubMedCrossRefGoogle Scholar
  37. 37.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    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.PubMedCrossRefGoogle Scholar
  39. 39.
    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.PubMedCrossRefGoogle Scholar
  40. 40.
    Tanaka T, Umemori T, Endo S, Muramatsu S, Kanemaki M, Kamimura Y, et al. Sld7, an Sld3-associated protein required for efficient chromosomal DNA replication in budding yeast. EMBO J. 2011;30(10):2019–30.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Bochman ML, Schwacha A. The Mcm2-7 complex has in vitro helicase activity. Mol Cell. 2008;31(2):287–93.PubMedCrossRefGoogle Scholar
  42. 42.
    Moyer SE, Lewis PW, Botchan MR. Isolation of the Cdc45/Mcm2-7/GINS (CMG) complex, a candidate for the eukaryotic DNA replication fork helicase. Proc Natl Acad Sci U S A. 2006;103(27):10236–41.PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Fu YV, Yardimci H, Long DT, Ho TV, Guainazzi A, Bermudez VP, et al. Selective bypass of a lagging strand roadblock by the eukaryotic replicative DNA helicase. Cell. 2011;146(6):931–41.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    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(2):1210–21.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Hart EA, Bryant JA, Moore K, Aves SJ. Fission yeast Cdc23 interactions with DNA replication initiation proteins. Curr Genet. 2002;41(5):342–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Homesley L, Lei M, Kawasaki Y, Sawyer S, Christensen T, Tye BK. Mcm10 and the MCM2-7 complex interact to initiate DNA synthesis and to release replication factors from origins. Genes Dev. 2000;14(8):913–26.PubMedCentralPubMedGoogle Scholar
  48. 48.
    Lee JK, Seo YS, Hurwitz J. The Cdc23 (Mcm10) protein is required for the phosphorylation of minichromosome maintenance complex by the Dfp1-Hsk1 kinase. Proc Natl Acad Sci U S A. 2003;100(5):2334–9.PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Sawyer SL, Cheng IH, Chai W, Tye BK. Mcm10 and Cdc45 cooperate in origin activation in Saccharomyces cerevisiae. J Mol Biol. 2004;340(2):195–202.PubMedCrossRefGoogle Scholar
  50. 50.
    Kawasaki Y, Hiraga S, Sugino A. Interactions between Mcm10p and other replication factors are required for proper initiation and elongation of chromosomal DNA replication in Saccharomyces cerevisiae. Genes Cells. 2000;5(12):975–89.PubMedCrossRefGoogle Scholar
  51. 51.
    Xu X, Rochette PJ, Feyissa EA, Su TV, Liu Y. MCM10 mediates RECQ4 association with MCM2-7 helicase complex during DNA replication. EMBO J. 2009;28(19):3005–14.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Araki Y, Kawasaki Y, Sasanuma H, Tye BK, Sugino A. Budding yeast mcm10/dna43 mutant requires a novel repair pathway for viability. Genes Cells. 2003;8(5):465–80.PubMedCrossRefGoogle Scholar
  53. 53.
    Izumi M, Yatagai F, Hanaoka F. Cell cycle-dependent proteolysis and phosphorylation of human Mcm10. J Biol Chem. 2001;276(51):48526–31.PubMedGoogle Scholar
  54. 54.
    Kaur M, Sharma A, Khan M, Kar A, Saxena S. Mcm10 proteolysis initiates before the onset of M-phase. BMC Cell Biol. 2010;11:84.PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Sharma A, Kaur M, Kar A, Ranade SM, Saxena S. Ultraviolet radiation stress triggers the down-regulation of essential replication factor Mcm10. J Biol Chem. 2010;285(11):8352–62.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Lan W, Chen S, Tong L. MicroRNA-215 regulates fibroblast function: insights from a human fibrotic disease. Cell Cycle. 2015;14(12):1973–84.Google Scholar
  57. 57.
    Yoshida K, Inoue I. Expression of MCM10 and TopBP1 is regulated by cell proliferation and UV irradiation via the E2F transcription factor. Oncogene. 2004;23(37):6250–60.PubMedCrossRefGoogle Scholar
  58. 58.
    Watase G, Takisawa H, Kanemaki MT. Mcm10 plays a role in functioning of the eukaryotic replicative DNA helicase, Cdc45-Mcm-GINS. Curr Biol. 2012;22(4):343–9.PubMedCrossRefGoogle Scholar
  59. 59.
    Gambus A, van Deursen F, Polychronopoulos D, Foltman M, Jones RC, Edmondson RD, et al. A key role for Ctf4 in coupling the MCM2-7 helicase to DNA polymerase alpha within the eukaryotic replisome. EMBO J. 2009;28(19):2992–3004.PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Gregan J, Lindner K, Brimage L, Franklin R, Namdar M, Hart EA, et al. Fission yeast Cdc23/Mcm10 functions after pre-replicative complex formation to promote Cdc45 chromatin binding. Mol Biol Cell. 2003;14(9):3876–87.PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Im JS, Ki SH, Farina A, Jung DS, Hurwitz J, Lee JK. 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. 2009;106(37):15628–32.PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Im JS, Park SY, Cho WH, Bae SH, Hurwitz J, Lee JK. RecQL4 is required for the association of Mcm10 and Ctf4 with replication origins in human cells. Cell Cycle. 2015;14(7):1001–9.Google Scholar
  64. 64.
    On KF, Beuron F, Frith D, Snijders AP, Morris EP, Diffley JF. Prereplicative complexes assembled in vitro support origin-dependent and independent DNA replication. EMBO J. 2014;33(6):605–20.PubMedCentralPubMedCrossRefGoogle Scholar
  65. 65.
    Yeeles JT, Deegan TD, Janska A, Early A, Diffley JF. Regulated eukaryotic DNA replication origin firing with purified proteins. Nature. 2015;519(7544):431–5.Google Scholar
  66. 66.
    Donovan S, Harwood J, Drury LS, Diffley JF. Cdc6p-dependent loading of Mcm proteins onto pre-replicative chromatin in budding yeast. Proc Natl Acad Sci U S A. 1997;94(11):5611–6.PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Edwards MC, Tutter AV, Cvetic C, Gilbert CH, Prokhorova TA, Walter JC. MCM2-7 complexes bind chromatin in a distributed pattern surrounding the origin recognition complex in Xenopus egg extracts. J Biol Chem. 2002;277(36):33049–57.PubMedCrossRefGoogle Scholar
  68. 68.
    Lei M, Kawasaki Y, Tye BK. Physical interactions among Mcm proteins and effects of Mcm dosage on DNA replication in Saccharomyces cerevisiae. Mol Cell Biol. 1996;16(9):5081–90.PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Mahbubani HM, Chong JP, Chevalier S, Thommes P, Blow JJ. Cell cycle regulation of the replication licensing system: involvement of a Cdk-dependent inhibitor. J Cell Biol. 1997;136(1):125–35.PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Kanke M, Kodama Y, Takahashi TS, Nakagawa T, Masukata H. Mcm10 plays an essential role in origin DNA unwinding after loading of the CMG components. EMBO J. 2012;31(9):2182–94.PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    van Deursen F, Sengupta S, De Piccoli G, Sanchez-Diaz A, Labib K. Mcm10 associates with the loaded DNA helicase at replication origins and defines a novel step in its activation. EMBO J. 2012;31(9):2195–206.PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Yu C, Gan H, Han J, Zhou ZX, Jia S, Chabes A, et al. Strand-specific analysis shows protein binding at replication forks and PCNA unloading from lagging strands when forks stall. Mol Cell. 2014;56(4):551–63.PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Zhu W, Ukomadu C, Jha S, Senga T, Dhar SK, Wohlschlegel JA, et al. Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication. Genes Dev. 2007;21(18):2288–99.PubMedCentralPubMedCrossRefGoogle Scholar
  74. 74.
    Yang X, Gregan J, Lindner K, Young H, Kearsey SE. Nuclear distribution and chromatin association of DNA polymerase alpha-primase is affected by TEV protease cleavage of Cdc23 (Mcm10) in fission yeast. BMC Mol Biol. 2005;6:13.PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Kunkel TA, Burgers PM. Dividing the workload at a eukaryotic replication fork. Trends Cell Biol. 2008;18(11):521–7.PubMedCentralPubMedCrossRefGoogle Scholar
  76. 76.
    Nick McElhinny SA, Gordenin DA, Stith CM, Burgers PM, Kunkel TA. Division of labor at the eukaryotic replication fork. Mol Cell. 2008;30(2):137–44.PubMedCentralPubMedCrossRefGoogle Scholar
  77. 77.
    Pacek M, Tutter AV, Kubota Y, Takisawa H, Walter JC. Localization of MCM2-7, Cdc45, and GINS to the site of DNA unwinding during eukaryotic DNA replication. Mol Cell. 2006;21(4):581–7.PubMedCrossRefGoogle Scholar
  78. 78.
    Alabert C, Bukowski-Wills JC, Lee SB, Kustatscher G, Nakamura K, de Lima Alves F, et al. Nascent chromatin capture proteomics determines chromatin dynamics during DNA replication and identifies unknown fork components. Nat Cell Biol. 2014;16(3):281–93.PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    Aparicio OM, Weinstein DM, Bell SP. Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase. Cell. 1997;91(1):59–69.PubMedCrossRefGoogle Scholar
  80. 80.
    Taylor M, Moore K, Murray J, Aves SJ, Price C. Mcm10 interacts with Rad4/Cut5(TopBP1) and its association with origins of DNA replication is dependent on Rad4/Cut5(TopBP1). DNA Repair (Amst). 2011;10(11):1154–63.CrossRefGoogle Scholar
  81. 81.
    Nasheuer HP, Grosse F. Immunoaffinity-purified DNA polymerase alpha displays novel properties. Biochemistry. 1987;26(25):8458–66.PubMedCrossRefGoogle Scholar
  82. 82.
    Kouprina N, Kroll E, Bannikov V, Bliskovsky V, Gizatullin R, Kirillov A, et al. CTF4 (CHL15) mutants exhibit defective DNA metabolism in the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1992;12(12):5736–47.PubMedCentralPubMedCrossRefGoogle Scholar
  83. 83.
    Apger J, Reubens M, Henderson L, Gouge CA, Ilic N, Zhou HH, et al. Multiple functions for Drosophila Mcm10 suggested through analysis of two Mcm10 mutant alleles. Genetics. 2010;185(4):1151–65.PubMedCentralPubMedCrossRefGoogle Scholar
  84. 84.
    Gosnell JA, Christensen TW. Drosophila Ctf4 is essential for efficient DNA replication and normal cell cycle progression. BMC Mol Biol. 2011;12:13.PubMedCentralPubMedCrossRefGoogle Scholar
  85. 85.
    Chattopadhyay S, Bielinsky AK. Human Mcm10 regulates the catalytic subunit of DNA polymerase-alpha and prevents DNA damage during replication. Mol Biol Cell. 2007;18(10):4085–95.PubMedCentralPubMedCrossRefGoogle Scholar
  86. 86.
    Haworth J, Alver RC, Anderson M, Bielinsky AK. Ubc4 and Not4 regulate steady-state levels of DNA polymerase-alpha to promote efficient and accurate DNA replication. Mol Biol Cell. 2010;21(18):3205–19.PubMedCentralPubMedCrossRefGoogle Scholar
  87. 87.
    Lee C, Liachko I, Bouten R, Kelman Z, Tye BK. Alternative mechanisms for coordinating polymerase alpha and MCM helicase. Mol Cell Biol. 2010;30(2):423–35.PubMedCentralPubMedCrossRefGoogle Scholar
  88. 88.
    Wang J, Wu R, Lu Y, Liang C. Ctf4p facilitates Mcm10p to promote DNA replication in budding yeast. Biochem Biophys Res Commun. 2010;395(3):336–41.PubMedCrossRefGoogle Scholar
  89. 89.
    Wawrousek KE, Fortini BK, Polaczek P, Chen L, Liu Q, Dunphy WG, et al. Xenopus DNA2 is a helicase/nuclease that is found in complexes with replication proteins And-1/Ctf4 and Mcm10 and DSB response proteins Nbs1 and ATM. Cell Cycle. 2010;9(6):1156–66.PubMedCentralPubMedCrossRefGoogle Scholar
  90. 90.
    Simon AC, Zhou JC, Perera RL, van Deursen F, Evrin C, Ivanova ME, et al. A Ctf4 trimer couples the CMG helicase to DNA polymerase alpha in the eukaryotic replisome. Nature. 2014;510(7504):293–7.PubMedCentralPubMedCrossRefGoogle Scholar
  91. 91.
    Fumasoni M, Zwicky K, Vanoli F, Lopes M, Branzei D. Error-free DNA damage tolerance and sister chromatid proximity during DNA replication rely on the Polalpha/Primase/Ctf4 complex. Mol Cell. 2015;57(5):812–23.Google Scholar
  92. 92.
    Kim S, Dallmann HG, McHenry CS, Marians KJ. tau couples the leading- and lagging-strand polymerases at the Escherichia coli DNA replication fork. J Biol Chem. 1996;271(35):21406–12.PubMedCrossRefGoogle Scholar
  93. 93.
    Kim S, Dallmann HG, McHenry CS, Marians KJ. Coupling of a replicative polymerase and helicase: a tau-DnaB interaction mediates rapid replication fork movement. Cell. 1996;84(4):643–50.PubMedCrossRefGoogle Scholar
  94. 94.
    Kurth I, O’Donnell M. New insights into replisome fluidity during chromosome replication. Trends Biochem Sci. 2013;38(4):195–203.PubMedCentralPubMedCrossRefGoogle Scholar
  95. 95.
    Dalrymple BP, Kongsuwan K, Wijffels G, Dixon NE, Jennings PA. A universal protein-protein interaction motif in the eubacterial DNA replication and repair systems. Proc Natl Acad Sci U S A. 2001;98(20):11627–32.PubMedCentralPubMedCrossRefGoogle Scholar
  96. 96.
    Thu YM, Bielinsky AK. MCM10: one tool for all-Integrity, maintenance and damage control. Semin Cell Dev Biol. 2014;30:121–30.PubMedCrossRefGoogle Scholar
  97. 97.
    Ellison V, Stillman B. Biochemical characterization of DNA damage checkpoint complexes: clamp loader and clamp complexes with specificity for 5′ recessed DNA. PLoS Biol. 2003;1(2):E33.PubMedCentralPubMedCrossRefGoogle Scholar
  98. 98.
    Majka J, Binz SK, Wold MS, Burgers PM. Replication protein A directs loading of the DNA damage checkpoint clamp to 5′-DNA junctions. J Biol Chem. 2006;281(38):27855–61.PubMedCrossRefGoogle Scholar
  99. 99.
    Becker JR, Nguyen HD, Wang X, Bielinsky AK. Mcm10 deficiency causes defective-replisome-induced mutagenesis and a dependency on error-free postreplicative repair. Cell Cycle. 2014;13(11):1737–48.PubMedCentralPubMedCrossRefGoogle Scholar
  100. 100.
    Miotto B, Chibi M, Xie P, Koundrioukoff S, Moolman-Smook H, Pugh D, et al. The RBBP6/ZBTB38/MCM10 axis regulates DNA replication and common fragile site stability. Cell Rep. 2014;7(2):575–87.PubMedCrossRefGoogle Scholar
  101. 101.
    Davies SL, North PS, Hickson ID. Role for BLM in replication-fork restart and suppression of origin firing after replicative stress. Nat Struct Mol Biol. 2007;14(7):677–9.PubMedCrossRefGoogle Scholar
  102. 102.
    Rosenberg C, Florijn RJ, Van de Rijke FM, Blonden LA, Raap TK, Van Ommen GJ, et al. High resolution DNA fiber-fish on yeast artificial chromosomes: direct visualization of DNA replication. Nat Genet. 1995;10(4):477–9.PubMedCrossRefGoogle Scholar
  103. 103.
    Kawabata T, Luebben SW, Yamaguchi S, Ilves I, Matise I, Buske T, et al. Stalled fork rescue via dormant replication origins in unchallenged S phase promotes proper chromosome segregation and tumor suppression. Mol Cell. 2011;41(5):543–53.PubMedCentralPubMedCrossRefGoogle Scholar
  104. 104.
    Woodward AM, Gohler T, Luciani MG, Oehlmann M, Ge X, Gartner A, et al. Excess Mcm2-7 license dormant origins of replication that can be used under conditions of replicative stress. J Cell Biol. 2006;173(5):673–83.PubMedCentralPubMedCrossRefGoogle Scholar
  105. 105.
    Lukas C, Savic V, Bekker-Jensen S, Doil C, Neumann B, Pedersen RS, et al. 53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress. Nat Cell Biol. 2011;13(3):243–53.PubMedCrossRefGoogle Scholar
  106. 106.
    Paulsen RD, Soni DV, Wollman R, Hahn AT, Yee MC, Guan A, et al. A genome-wide siRNA screen reveals diverse cellular processes and pathways that mediate genome stability. Mol Cell. 2009;35(2):228–39.PubMedCentralPubMedCrossRefGoogle Scholar
  107. 107.
    Park JH, Bang SW, Jeon Y, Kang S, Hwang DS. Knockdown of human MCM10 exhibits delayed and incomplete chromosome replication. Biochem Biophys Res Commun. 2008;365(3):575–82.PubMedCrossRefGoogle Scholar
  108. 108.
    Park JH, Bang SW, Kim SH, Hwang DS. Knockdown of human MCM10 activates G2 checkpoint pathway. Biochem Biophys Res Commun. 2008;365(3):490–5.PubMedCrossRefGoogle Scholar
  109. 109.
    Tittel-Elmer M, Alabert C, Pasero P, Cobb JA. The MRX complex stabilizes the replisome independently of the S phase checkpoint during replication stress. EMBO J. 2009;28(8):1142–56.PubMedCentralPubMedCrossRefGoogle Scholar
  110. 110.
    Wu C, Zhu J, Zhang X. Integrating gene expression and protein-protein interaction network to prioritize cancer-associated genes. BMC Bioinformatics. 2012;13:182.PubMedCentralPubMedCrossRefGoogle Scholar
  111. 111.
    Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2(5):401–4.PubMedCrossRefGoogle Scholar
  112. 112.
    Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6(269):l1.CrossRefGoogle Scholar
  113. 113.
    Kang G, Hwang WC, Do IG, Wang K, Kang SY, Lee J, et al. Exome sequencing identifies early gastric carcinoma as an early stage of advanced gastric cancer. PLoS One. 2013;8(12):e82770.PubMedCentralPubMedCrossRefGoogle Scholar
  114. 114.
    Halazonetis TD, Gorgoulis VG, Bartek J. An oncogene-induced DNA damage model for cancer development. Science. 2008;319(5868):1352–5.PubMedCrossRefGoogle Scholar
  115. 115.
    Burrell RA, McClelland SE, Endesfelder D, Groth P, Weller MC, Shaikh N, et al. Replication stress links structural and numerical cancer chromosomal instability. Nature. 2013;494(7438):492–6.PubMedCentralPubMedCrossRefGoogle Scholar
  116. 116.
    Garcia-Aragoncillo E, Carrillo J, Lalli E, Agra N, Gomez-Lopez G, Pestana A, et al. DAX1, a direct target of EWS/FLI1 oncoprotein, is a principal regulator of cell-cycle progression in Ewing’s tumor cells. Oncogene. 2008;27(46):6034–43.PubMedCrossRefGoogle Scholar
  117. 117.
    Koppen A, Ait-Aissa R, Koster J, van Sluis PG, Ora I, Caron HN, et al. Direct regulation of the minichromosome maintenance complex by MYCN in neuroblastoma. Eur J Cancer. 2007;43(16):2413–22.PubMedCrossRefGoogle Scholar
  118. 118.
    Das M, Prasad SB, Yadav SS, Govardhan HB, Pandey LK, Singh S, et al. Over expression of minichromosome maintenance genes is clinically correlated to cervical carcinogenesis. PLoS One. 2013;8(7):e69607.PubMedCentralPubMedCrossRefGoogle Scholar
  119. 119.
    Nijhawan D, Zack TI, Ren Y, Strickland MR, Lamothe R, Schumacher SE, et al. Cancer vulnerabilities unveiled by genomic loss. Cell. 2012;150(4):842–54.PubMedCentralPubMedCrossRefGoogle Scholar
  120. 120.
    Liachko I, Tye BK. Mcm10 is required for the maintenance of transcriptional silencing in Saccharomyces cerevisiae. Genetics. 2005;171(2):503–15.PubMedCentralPubMedCrossRefGoogle Scholar
  121. 121.
    Liachko I, Tye BK. Mcm10 mediates the interaction between DNA replication and silencing machineries. Genetics. 2009;181(2):379–91.PubMedCentralPubMedCrossRefGoogle Scholar
  122. 122.
    Vo N, Taga A, Inaba Y, Yoshida H, Cotterill S, Yamaguchi M. Drosophila Mcm10 is required for DNA replication and differentiation in the compound eye. PLoS One. 2014; 9(3):e93450.Google Scholar
  123. 123.
    Wang JT, Xu X, Alontaga AY, Chen Y, Liu Y. Impaired p32 regulation caused by the lymphoma-prone RECQ4 mutation drives mitochondrial dysfunction. Cell Rep. 2014;7(3):848–58.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Ryan M. Baxley
    • 1
  • Yee Mon Thu
    • 1
  • Anja-Katrin Bielinsky
    • 1
  1. 1.Biochemistry, Molecular Biology and BiophysicsUniversity of MinnesotaMinneapolisUSA

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