Table of Contents
Molecular Biology International
Volume 2014, Article ID 574850, 11 pages
http://dx.doi.org/10.1155/2014/574850
Review Article

MCM Paradox: Abundance of Eukaryotic Replicative Helicases and Genomic Integrity

1Cancer Genetics Laboratory, Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, India
2Department of Zoology, Mahila Mahavidyalaya College, Banaras Hindu University, Varanasi, India
3Department of Radiotherapy & Radiation Medicine, Banaras Hindu University, Varanasi, India

Received 29 August 2014; Accepted 30 September 2014; Published 19 October 2014

Academic Editor: Malayannan B. Subramaniam

Copyright © 2014 Mitali Das et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. L. Forsburg, “Eukaryotic MCM proteins: beyond replication initiation,” Microbiology and Molecular Biology Reviews, vol. 68, no. 1, pp. 109–131, 2004. View at Publisher · View at Google Scholar · View at Scopus
  2. G. T. Maine, P. Sinha, and B. W. Tye, “Mutants of S. cerevisiae defective in the maintenance of minichromosomes,” Genetics, vol. 106, no. 3, pp. 365–385, 1984. View at Google Scholar · View at Scopus
  3. P. Sinha, V. Chang, and B.-K. Tye, “A mutant that affects the functions of autonomously replicating sequences in yeast,” Journal of Molecular Biology, vol. 192, no. 4, pp. 805–814, 1986. View at Publisher · View at Google Scholar · View at Scopus
  4. B. K. Tye, “Minichromosome maintenance as a genetic assay for defects in DNA replication,” Methods, vol. 18, no. 3, pp. 329–334, 1999. View at Publisher · View at Google Scholar · View at Scopus
  5. B. K. Tye, “MCM proteins in DNA replication,” Annual Review of Biochemistry, vol. 68, pp. 649–686, 1999. View at Publisher · View at Google Scholar · View at Scopus
  6. H. Yan, S. Gibson, and B. K. Tye, “Mcm2 and Mcm37 two proteins important for ARS activity, are related in structure and function,” Genes & Development, vol. 5, no. 6, pp. 944–957, 1991. View at Publisher · View at Google Scholar · View at Scopus
  7. S. P. Bell and A. Dutta, “DNA replication in eukaryotic cells,” Annual Review of Biochemistry, vol. 71, pp. 333–374, 2002. View at Publisher · View at Google Scholar · View at Scopus
  8. J. P. J. Chong, H. M. Mahbubani, C. Y. Khoo, and J. J. Blow, “Purification of an MCM-containing complex as a component of the DNA replication licensing system,” Nature, vol. 375, no. 6530, pp. 418–421, 1995. View at Publisher · View at Google Scholar · View at Scopus
  9. S. Dalton and B. Hopwood, “Characterization of Cdc47p-minichromosome maintenance complexes in Saccharomyces cerevisiae: identification of Cdc45p as a subunit,” Molecular and Cellular Biology, vol. 17, no. 10, pp. 5867–5875, 1997. View at Google Scholar · View at Scopus
  10. M. Lei, Y. Kawasaki, and B. K. Tye, “Physical interactions among Mcm proteins and effects of Mcm dosage on DNA replication in Saccharomyces cerevisiae,” Molecular and Cellular Biology, vol. 16, no. 9, pp. 5081–5090, 1996. View at Google Scholar · View at Scopus
  11. Y. Adachi, J. Usukura, and M. Yanagida, “A globular complex formation by Nda1 and the other five members of the MCM protein family in fission yeast,” Genes to Cells, vol. 2, no. 7, pp. 467–479, 1997. View at Publisher · View at Google Scholar · View at Scopus
  12. Z. You, Y. Komamura, and Y. Ishimi, “Biochemical analysis of the intrinsic Mcm4-Mcm6-Mcm7 DNA helicase activity,” Molecular and Cellular Biology, vol. 19, no. 12, pp. 8003–8015, 1999. View at Google Scholar · View at Scopus
  13. Y. Ishimi and Y. Komamura-Kohno, “Phosphorylation of Mcm4 at specific sites by cyclin -dependent kinase leads to loss of Mcm4,6,7 helicase activity,” Journal of Biological Chemistry, vol. 276, no. 37, pp. 34428–34433, 2001. View at Publisher · View at Google Scholar · View at Scopus
  14. J.-K. Lee and J. Hurwitz, “Processive DNA helicase activity of the minichromosome maintenance proteins 4, 6, and 7 complex requires forked DNA structures,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 1, pp. 54–59, 2001. View at Publisher · View at Google Scholar · View at Scopus
  15. M. Foltman, C. Evrin, G. de Piccoli et al., “Eukaryotic replisome components cooperate to process histones during chromosome replication,” Cell Reports, vol. 3, no. 3, pp. 892–904, 2013. View at Publisher · View at Google Scholar · View at Scopus
  16. M. A. Madine, C.-Y. Khoo, A. D. Mills, and R. A. Laskey, “MCM3 complex required for cell cycle regulation of DNA replication in vertebrate cells,” Nature, vol. 375, no. 6530, pp. 421–424, 1995. View at Publisher · View at Google Scholar · View at Scopus
  17. Y. Kubota, S. Mimura, S.-I. Nishimoto, T. Masuda, H. Nojima, and H. Takisawa, “Licensing of DNA replication by a multi-protein complex of MCM/P1 proteins in Xenopus eggs,” The EMBO Journal, vol. 16, no. 11, pp. 3320–3331, 1997. View at Publisher · View at Google Scholar · View at Scopus
  18. J. J. Blow, S. M. Dilworth, C. Dingwall, A. D. Mills, and R. A. Laskey, “Chromosome replication in cell-free systems from Xenopus eggs,” Philosophical transactions of the Royal Society of London Series B: Biological sciences, vol. 317, no. 1187, pp. 483–494, 1987. View at Publisher · View at Google Scholar · View at Scopus
  19. K. M. Hennessy, C. D. Clark, and D. Botstein, “Subcellular localization of yeast CDC46 varies with the cell cycle,” Genes and Development, vol. 4, no. 12, pp. 2252–2263, 1990. View at Publisher · View at Google Scholar · View at Scopus
  20. R. Laskey, “The Croonian Lecture 2001 hunting the antisocial cancer cell: MCM proteins and their exploitation,” Philosophical Transactions of the Royal Society B: Biological Sciences, vol. 360, no. 1458, pp. 1119–1132, 2005. View at Publisher · View at Google Scholar · View at Scopus
  21. T. J. Takara and S. P. Bell, “Multiple Cdt1 molecules act at each origin to load replication-competent Mcm2–7 helicases,” The EMBO Journal, vol. 30, no. 24, pp. 4885–4896, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. L. Wu, Y. Liu, and D. Kong, “Mechanism of chromosomal DNA replication initiation and replication fork stabilization in eukaryotes,” Science China Life Sciences, vol. 57, no. 5, pp. 482–487, 2014. View at Publisher · View at Google Scholar · View at Scopus
  23. K. Labib and J. F. X. Diffley, “Is the MCM2-7 complex the eukaryotic DNA replication fork helicase?” Current Opinion in Genetics and Development, vol. 11, no. 1, pp. 64–70, 2001. View at Publisher · View at Google Scholar · View at Scopus
  24. Y. Ishimi, “A DNA helicase activity is associated with an MCM4, -6, and -7 protein complex,” The Journal of Biological Chemistry, vol. 272, no. 39, pp. 24508–24513, 1997. View at Publisher · View at Google Scholar · View at Scopus
  25. M. L. Bochman and A. Schwacha, “The Mcm2-7 complex has in vitro helicase activity,” Molecular Cell, vol. 31, no. 2, pp. 287–293, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. D. Boos, J. Frigola, and J. F. X. Diffley, “Activation of the replicative DNA helicase: breaking up is hard to do,” Current Opinion in Cell Biology, vol. 24, no. 3, pp. 423–430, 2012. View at Publisher · View at Google Scholar · View at Scopus
  27. Y.-H. Kang, W. C. Galal, A. Farina, I. Tappin, and J. Hurwitz, “Properties of the human Cdc45/Mcm2-7/GINS helicase complex and its action with DNA polymerase ε in rolling circle DNA synthesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 16, pp. 6042–6047, 2012. View at Publisher · View at Google Scholar · View at Scopus
  28. Y.-H. Kang, A. Farina, V. P. Bermudez et al., “Interaction between human Ctf4 and the Cdc45/Mcm2-7/GINS (CMG) replicative helicase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 49, pp. 19760–19765, 2013. View at Publisher · View at Google Scholar · View at Scopus
  29. A. Costa and S. Onesti, “Structural biology of MCM helicases,” Critical Reviews in Biochemistry and Molecular Biology, vol. 44, no. 5, pp. 326–342, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. Z. Kelman, J. K. Lee, and J. Hurwitz, “The single minichromosome maintenance protein of Methanobacterium thermoautotrophicum ΔH contains DNA helicase activity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 26, pp. 14783–14788, 1999. View at Publisher · View at Google Scholar · View at Scopus
  31. D. F. Shechter, C. Y. Ying, and J. Gautier, “The intrinsic DNA helicase activity of Methanobacterium thermoautotrophicum ΔH minichromosome maintenance protein,” The Journal of Biological Chemistry, vol. 275, no. 20, pp. 15049–15059, 2000. View at Publisher · View at Google Scholar · View at Scopus
  32. J. P. J. Chong, M. K. Hayashi, M. N. Simon, R.-M. Xu, and B. Stillman, “A double-hexamer archaeal minichromosome maintenance protein is an ATP-dependent DNA helicase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 4, pp. 1530–1535, 2000. View at Publisher · View at Google Scholar · View at Scopus
  33. R. J. Fletcher, B. E. Bishop, R. P. Leon, R. A. Sclafani, C. M. Ogata, and X. S. Chen, “The structure and function of MCM from archaeal M. thermoautotrophicum,” Nature Structural Biology, vol. 10, no. 3, pp. 160–167, 2003. View at Publisher · View at Google Scholar · View at Scopus
  34. F. Carpentieri, M. de Felice, M. de Falco, M. Rossi, and F. M. Pisani, “Physical and functional interaction between the mini-chromosome maintenance-like DNA helicase and the single-stranded DNA binding protein from the crenarchaeon Sulfolobus solfataricus,” The Journal of Biological Chemistry, vol. 277, no. 14, pp. 12118–12127, 2002. View at Publisher · View at Google Scholar · View at Scopus
  35. A. Y. Lyubimov, M. Strycharska, and J. M. Berger, “The nuts and bolts of ring-translocase structure and mechanism,” Current Opinion in Structural Biology, vol. 21, no. 2, pp. 240–248, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. O. M. Aparicio, D. M. Weinstein, and S. P. Bell, “Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase,” Cell, vol. 91, no. 1, pp. 59–69, 1997. View at Publisher · View at Google Scholar · View at Scopus
  37. A. Gambus, R. C. Jones, A. Sanchez-Diaz et al., “GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks,” Nature Cell Biology, vol. 8, no. 4, pp. 358–366, 2006. View at Publisher · View at Google Scholar · View at Scopus
  38. M. Pacek, A. V. Tutter, Y. Kubota, H. Takisawa, and J. C. Walter, “Localization of MCM2-7, Cdc45, and GINS to the site of DNA unwinding during eukaryotic DNA replication,” Molecular Cell, vol. 21, no. 4, pp. 581–587, 2006. View at Publisher · View at Google Scholar · View at Scopus
  39. T. Aparicio, E. Guillou, J. Coloma, G. Montoya, and J. Méndez, “The human GINS complex associates with Cdc45 and MCM and is essential for DNA replication,” Nucleic Acids Research, vol. 37, no. 7, pp. 2087–2095, 2009. View at Publisher · View at Google Scholar · View at Scopus
  40. A. Gambus, G. A. Khoudoli, R. C. Jones, and J. J. Blow, “MCM2-7 form double hexamers at licensed origins in Xenopus egg extract,” The Journal of Biological Chemistry, vol. 286, no. 13, pp. 11855–11864, 2011. View at Publisher · View at Google Scholar · View at Scopus
  41. J.-S. Im, S.-H. Ki, A. Farina, D.-S. Jung, J. Hurwitz, and J.-K. Lee, “Assembly of the Cdc45-Mcm2-7-GINS complex in human cells requires the Ctf4/And-1, RecQL4, and Mcm10 proteins,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 37, pp. 15628–15632, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. K. Labib, J. A. Tercero, and J. F. X. Diffley, “Uninterrupted MCH2-7 function required for DNA replication fork progression,” Science, vol. 288, no. 5471, pp. 1643–1647, 2000. View at Publisher · View at Google Scholar · View at Scopus
  43. M. Pacek and J. C. Walter, “A requirement for MCM7 and Cdc45 in chromosome unwinding during eukaryotic DNA replication,” The EMBO Journal, vol. 23, no. 18, pp. 3667–3676, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. O. Hyrien, K. Marheineke, and A. Goldar, “Paradoxes of eukaryotic DNA replication: MCM proteins and the random completion problem,” BioEssays, vol. 25, no. 2, pp. 116–125, 2003. View at Publisher · View at Google Scholar · View at Scopus
  45. M. A. Madine, A. D. Mills, C. Musahl, and R. A. Laskey, “The nuclear envelope prevents reinitiation of replication by regulating the binding of MCM3 to chromatin in Xenopus egg extracts,” Current Biology, vol. 5, no. 11, pp. 1270–1279, 1995. View at Publisher · View at Google Scholar · View at Scopus
  46. T. Krude, C. Musahl, R. A. Laskey, and R. Knippers, “Human replication proteins hCdc21, hCdc46 and P1Mcm3 bind chromatin uniformly before S-phase and are displaced locally during DNA replication,” Journal of Cell Science, vol. 109, no. 2, pp. 309–318, 1996. View at Google Scholar · View at Scopus
  47. D. S. Dimitrova, I. T. Todorov, T. Melendy, and D. M. Gilbert, “Mcm2, but not RPA, is a component of the mammalian early G1-phase prereplication complex,” The Journal of Cell Biology, vol. 146, no. 4, pp. 709–722, 1999. View at Publisher · View at Google Scholar · View at Scopus
  48. M. Mašata, J. Malínský, H. Fidlerová, E. Smirnov, and I. Raška, “Dynamics of replication foci in early S phase as visualized by cross-correlation function,” Journal of Structural Biology, vol. 151, no. 1, pp. 61–68, 2005. View at Publisher · View at Google Scholar · View at Scopus
  49. I.-E. Symeonidou, P. Kotsantis, V. Roukos et al., “Multi-step loading of human minichromosome maintenance proteins in live human cells,” The Journal of Biological Chemistry, vol. 288, no. 50, pp. 35852–35867, 2013. View at Publisher · View at Google Scholar · View at Scopus
  50. D. M. Gilbert, “Making sense of eukaryotic DNA replication origins,” Science, vol. 294, no. 5540, pp. 96–100, 2001. View at Publisher · View at Google Scholar · View at Scopus
  51. H. Kimura, N. Nozaki, and K. Sugimoto, “DNA polymerase α associated protein P1, a murine homolog of yeast MCM3, changes its intranuclear distribution during the DNA synthetic period,” The EMBO Journal, vol. 13, no. 18, pp. 4311–4320, 1994. View at Google Scholar · View at Scopus
  52. R. Burkhart, D. Schulte, B. Hu, C. Musahl, F. Gohring, and R. Knippers, “Interactions of human nuclear proteins P1Mcm3 and P1Cdc46,” European Journal of Biochemistry, vol. 228, no. 2, pp. 431–438, 1995. View at Publisher · View at Google Scholar · View at Scopus
  53. S. Donovan, J. Harwood, L. S. Drury, and J. F. X. Diffley, “Cdc6p-dependent loading of Mcm proteins onto pre-replicative chromatin in budding yeast,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 11, pp. 5611–5616, 1997. View at Publisher · View at Google Scholar · View at Scopus
  54. A. Richter and R. Knippers, “High-molecular-mass complexes of human minichromosome-maintenance proteins in mitotic cells,” European Journal of Biochemistry, vol. 247, no. 1, pp. 136–141, 1997. View at Publisher · View at Google Scholar · View at Scopus
  55. M. Ritzi, M. Baack, C. Musahl, P. Romanowski, R. A. Laskey, and R. Knippers, “Human minichromosome maintenance proteins and human origin recognition complex 2 protein on chromatin,” The Journal of Biological Chemistry, vol. 273, no. 38, pp. 24543–24549, 1998. View at Publisher · View at Google Scholar · View at Scopus
  56. H. M. Mahbubani, J. P. J. Chong, S. Chevalier, P. Thömmes, and J. J. Blow, “Cell cycle regulation of the replication licensing system: involvement of a Cdk-dependent inhibitor,” The Journal of Cell Biology, vol. 136, no. 1, pp. 125–135, 1997. View at Publisher · View at Google Scholar · View at Scopus
  57. J. Walter and J. W. Newport, “Regulation of replicon size in Xenopus egg extracts,” Science, vol. 275, no. 5302, pp. 993–995, 1997. View at Publisher · View at Google Scholar · View at Scopus
  58. M. C. Edwards, A. V. Tutter, C. Cvetic, C. H. Gilbert, T. A. Prokhorova, and J. C. Walter, “MCM2-7 complexes bind chromatin in a distributed pattern surrounding the origin recognition complex in Xenopus egg extracts,” The Journal of Biological Chemistry, vol. 277, no. 36, pp. 33049–33057, 2002. View at Publisher · View at Google Scholar · View at Scopus
  59. T. Aparicio, D. Megías, and J. Méndez, “Visualization of the MCM DNA helicase at replication factories before the onset of DNA synthesis,” Chromosoma, vol. 121, no. 5, pp. 499–507, 2012. View at Publisher · View at Google Scholar · View at Scopus
  60. M. A. Kuipers, T. J. Stasevich, T. Sasaki et al., “Highly stable loading of Mcm proteins onto chromatin in living cells requires replication to unload,” The Journal of Cell Biology, vol. 192, no. 1, pp. 29–41, 2011. View at Publisher · View at Google Scholar · View at Scopus
  61. R. A. Laskey and M. A. Madine, “A rotary pumping model for helicase function of MCM proteins at a distance from replication forks,” The EMBO Reports, vol. 4, no. 1, pp. 26–30, 2003. View at Publisher · View at Google Scholar · View at Scopus
  62. T. S. Takahashi, D. B. Wigley, and J. C. Walter, “Pumps, paradoxes and ploughshares: mechanism of the MCM2-7 DNA helicase,” Trends in Biochemical Sciences, vol. 30, no. 8, pp. 437–444, 2005. View at Publisher · View at Google Scholar · View at Scopus
  63. M. Mašata, P. Juda, O. Raška, M. C. Cardoso, and I. Raška, “A fraction of MCM 2 proteins remain associated with replication foci during a major part of S phase,” Folia Biologica, vol. 57, no. 1, pp. 3–11, 2011. View at Google Scholar · View at Scopus
  64. E. Guillou, A. Ibarra, V. Coulon et al., “Cohesin organizes chromatin loops at DNA replication factories,” Genes and Development, vol. 24, no. 24, pp. 2812–2822, 2010. View at Publisher · View at Google Scholar · View at Scopus
  65. A. Nishiyama, L. Frappier, and M. Méchali, “MCM-BP regulates unloading of the MCM2-7 helicase in late S phase,” Genes & Development, vol. 25, no. 2, pp. 165–175, 2011. View at Publisher · View at Google Scholar · View at Scopus
  66. D. Cortez, G. Glick, and S. J. Elledge, “Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 27, pp. 10078–10083, 2004. View at Publisher · View at Google Scholar · View at Scopus
  67. C.-C. Tsao, C. Geisen, and R. T. Abraham, “Interaction between human MCM7 and Rad17 proteins is required for replication checkpoint signaling,” The EMBO Journal, vol. 23, no. 23, pp. 4660–4669, 2004. View at Publisher · View at Google Scholar · View at Scopus
  68. A. M. Woodward, T. Göhler, M. G. Luciani et al., “Excess Mcm2-7 license dormant origins of replication that can be used under conditions of replicative stress,” The Journal of Cell Biology, vol. 173, no. 5, pp. 673–683, 2006. View at Publisher · View at Google Scholar · View at Scopus
  69. R. C. Alver, G. S. Chadha, and J. J. Blow, “The contribution of dormant origins to genome stability: from cell biology to human genetics,” DNA Repair, vol. 19, no. 9, pp. 182–189, 2014. View at Publisher · View at Google Scholar · View at Scopus
  70. X. Q. Ge, D. A. Jackson, and J. J. Blow, “Dormant origins licensed by excess Mcm2-7 are required for human cells to survive replicative stress,” Genes & Development, vol. 21, no. 24, pp. 3331–3341, 2007. View at Publisher · View at Google Scholar · View at Scopus
  71. A. Ibarra, E. Schwob, and J. Méndez, “Excess MCM proteins protect human cells from replicative stress by licensing backup origins of replication,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 26, pp. 8956–8961, 2008. View at Publisher · View at Google Scholar · View at Scopus
  72. N. Shima, A. Alcaraz, I. Liachko et al., “A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice,” Nature Genetics, vol. 39, no. 1, pp. 93–98, 2007. View at Publisher · View at Google Scholar · View at Scopus
  73. C.-H. Chuang, M. D. Wallace, C. Abratte, T. Southard, and J. C. Schimenti, “Incremental genetic perturbations to MCM2-7 expression and subcellular distribution reveal exquisite sensitivity of mice to DNA replication stress,” PLoS Genetics, vol. 6, no. 9, Article ID e1001110, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. D. Kunnev, M. E. Rusiniak, A. Kudla, A. Freeland, G. K. Cady, and S. C. Pruitt, “DNA damage response and tumorigenesis in Mcm2-deficient mice,” Oncogene, vol. 29, no. 25, pp. 3630–3638, 2010. View at Publisher · View at Google Scholar · View at Scopus
  75. K. Maki, T. Inoue, A. Onaka et al., “Abundance of prereplicative complexes (Pre-RCs) facilitates recombinational repair under replication stress in fission yeast,” The Journal of Biological Chemistry, vol. 286, no. 48, pp. 41701–41710, 2011. View at Publisher · View at Google Scholar · View at Scopus
  76. J. J. Blow and A. Dutta, “Preventing re-replication of chromosomal DNA,” Nature Reviews Molecular Cell Biology, vol. 6, no. 6, pp. 476–486, 2005. View at Publisher · View at Google Scholar · View at Scopus
  77. E. E. Arias and J. C. Walter, “Strength in numbers: preventing rereplication via multiple mechanisms in eukaryotic cells,” Genes & Development, vol. 21, no. 5, pp. 497–518, 2007. View at Publisher · View at Google Scholar · View at Scopus
  78. J. J. Blow, X. Q. Ge, and D. A. Jackson, “How dormant origins promote complete genome replication,” Trends in Biochemical Sciences, vol. 36, no. 8, pp. 405–414, 2011. View at Publisher · View at Google Scholar · View at Scopus
  79. S. Ryu, J. Holzschuh, S. Erhardt, A.-K. Ettl, and W. Driever, “Depletion of minichromosome maintenance protein 5 in the zebrafish retina causes cell-cycle defect and apoptosis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 51, pp. 18467–18472, 2005. View at Publisher · View at Google Scholar · View at Scopus
  80. C. R. Hughes, L. Guasti, E. Meimaridou et al., “MCM4 mutation causes adrenal failure, short stature, and natural killer cell deficiency in humans,” The Journal of Clinical Investigation, vol. 122, no. 3, pp. 814–820, 2012. View at Publisher · View at Google Scholar · View at Scopus
  81. L. Gineau, C. Cognet, N. Kara et al., “Partial MCM4 deficiency in patients with growth retardation, adrenal insufficiency, and natural killer cell deficiency,” The Journal of Clinical Investigation, vol. 122, no. 3, pp. 821–832, 2012. View at Publisher · View at Google Scholar · View at Scopus
  82. B. N. Bagley, T. M. Keane, V. I. Maklakova et al., “A dominantly acting murine allele of Mcm4 causes chromosomal abnormalities and promotes tumorigenesis,” PLoS Genetics, vol. 8, no. 11, Article ID e1003034, 2012. View at Publisher · View at Google Scholar · View at Scopus
  83. S. C. Pruitt, K. J. Bailey, and A. Freeland, “Reduced Mcm2 expression results in severe stem/progenitor cell deficiency and cancer,” Stem Cells, vol. 25, no. 12, pp. 3121–3132, 2007. View at Publisher · View at Google Scholar · View at Scopus
  84. M. E. Rusiniak, D. Kunnev, A. Freeland, G. K. Cady, and S. C. Pruitt, “Mcm2 deficiency results in short deletions allowing high resolution identification of genes contributing to lymphoblastic lymphoma,” Oncogene, vol. 31, no. 36, pp. 4034–4044, 2012. View at Publisher · View at Google Scholar · View at Scopus
  85. B. Ren, G. Yu, G. C. Tseng et al., “MCM7 amplification and overexpression are associated with prostate cancer progression,” Oncogene, vol. 25, no. 7, pp. 1090–1098, 2006. View at Publisher · View at Google Scholar · View at Scopus
  86. C. Giaginis, M. Georgiadou, K. Dimakopoulou et al., “Clinical significance of MCM-2 and MCM-5 expression in colon cancer: association with clinicopathological parameters and tumor proliferative capacity,” Digestive Diseases and Sciences, vol. 54, no. 2, pp. 282–291, 2009. View at Publisher · View at Google Scholar · View at Scopus
  87. O. Saydam, O. Senol, T. B. M. Schaaij-Visser et al., “Comparative protein profiling reveals minichromosome maintenance (MCM) proteins as novel potential tumor markers for meningiomas,” Journal of Proteome Research, vol. 9, no. 1, pp. 485–494, 2010. View at Publisher · View at Google Scholar · View at Scopus
  88. U. Cobanoglu, S. Mungan, C. Gundogdu, S. Ersoz, Y. Ozoran, and F. Aydin, “The expression of MCM-2 in invasive breast carcinoma: a stereologic approach,” Bratislavské Lekárske Listy, vol. 111, no. 1, pp. 45–49, 2010. View at Google Scholar · View at Scopus
  89. K.-M. Lau, Q. K. Y. Chan, J. C. S. Pang et al., “Minichromosome maintenance proteins 2, 3 and 7 in medulloblastoma: overexpression and involvement in regulation of cell migration and invasion,” Oncogene, vol. 29, no. 40, pp. 5475–5489, 2010. View at Publisher · View at Google Scholar · View at Scopus
  90. C. Giaginis, A. Giagini, G. Tsourouflis et al., “MCM-2 and MCM-5 expression in gastric adenocarcinoma: clinical significance and comparison with Ki-67 proliferative marker,” Digestive Diseases and Sciences, vol. 56, no. 3, pp. 777–785, 2011. View at Publisher · View at Google Scholar · View at Scopus
  91. A. F. Nicol, J. R. Lapa e Silva, C. B. Cunha et al., “Evaluation of MCM-2 expression in TMA cervical specimens,” PLoS ONE, vol. 7, no. 4, Article ID e32936, 2012. View at Publisher · View at Google Scholar · View at Scopus
  92. M. Das, S. B. Prasad, S. S. Yadav et al., “Over expression of minichromosome maintenance genes is clinically correlated to cervical carcinogenesis,” PLoS ONE, vol. 8, no. 7, Article ID e69607, 2013. View at Publisher · View at Google Scholar · View at Scopus
  93. M. L. Kuijjer, H. Rydbeck, S. H. Kresse et al., “Identification of osteosarcoma driver genes by integrative analysis of copy number and gene expression data,” Genes Chromosomes and Cancer, vol. 51, no. 7, pp. 696–706, 2012. View at Publisher · View at Google Scholar · View at Scopus
  94. X. Zhong, X. Chen, X. Guan et al., “Overexpressions of G9a and MCM7 in Esophageal squamous cell carcinoma associated with poor prognosis,” Histopathology, 2014. View at Publisher · View at Google Scholar
  95. A. Freeman, L. S. Morris, A. D. Mills et al., “Minichromosome maintenance proteins as biological markers of dysplasia and malignancy,” Clinical Cancer Research, vol. 5, no. 8, pp. 2121–2132, 1999. View at Google Scholar · View at Scopus
  96. S. B. Wharton, K. K. Chan, J. R. Anderson, K. Stoeber, and G. H. Williams, “Replicative Mcm2 protein as a novel proliferation marker in oligodendrogliomas and its relationship to Ki67 labelling index, histological grade and prognosis,” Neuropathology and Applied Neurobiology, vol. 27, no. 4, pp. 305–313, 2001. View at Publisher · View at Google Scholar · View at Scopus
  97. K. Rodins, M. Cheale, N. Coleman, and S. B. Fox, “Minichromosome maintenance protein 2 expression in normal kidney and renal cell carcinomas: relationship to tumor dormancy and potential clinical utility,” Clinical Cancer Research, vol. 8, no. 4, pp. 1075–1081, 2002. View at Google Scholar · View at Scopus
  98. H. Kato, T. Miyazaki, Y. Fukai et al., “A new proliferation marker, minichromosome maintenance protein 2, is associated with tumor aggressiveness in esophageal squamous cell carcinoma,” Journal of Surgical Oncology, vol. 84, no. 1, pp. 24–30, 2003. View at Publisher · View at Google Scholar · View at Scopus
  99. P. Chatrath, I. S. Scott, L. S. Morris et al., “Aberrant expression of minichromosome maintenance protein-2 and Ki67 in laryngeal squamous epithelial lesions,” British Journal of Cancer, vol. 89, no. 6, pp. 1048–1054, 2003. View at Publisher · View at Google Scholar · View at Scopus
  100. M. A. Gonzalez, S. E. Pinder, G. Callagy et al., “Minichromosome maintenance protein 2 is a strong independent prognostic marker in breast cancer,” Journal of Clinical Oncology, vol. 21, no. 23, pp. 4306–4313, 2003. View at Publisher · View at Google Scholar · View at Scopus
  101. C. Kobierzycki, B. Pula, A. Wojnar, M. Podhorska-Okolow, and P. Dziegiel, “Tissue microarray technique in evaluation of proliferative activity in invasive ductal breast cancer,” Anticancer Research, vol. 32, no. 3, pp. 773–777, 2012. View at Google Scholar · View at Scopus
  102. E. C. Obermann, P. Went, A. Zimpfer et al., “Expression of minichromosome maintenance protein 2 as a marker for proliferation and prognosis in diffuse large B-cell lymphoma: a tissue microarray and clinico-pathological analysis,” BMC Cancer, vol. 5, article 162, 2005. View at Publisher · View at Google Scholar · View at Scopus
  103. J. Szelachowska, P. Dziegiel, J. Jelen-Krzeszewska et al., “Mcm-2 protein expression predicts prognosis better than Ki-67 antigen in oral cavity squamocellular carcinoma,” Anticancer Research, vol. 26, no. 3, pp. 2473–2478, 2006. View at Google Scholar · View at Scopus
  104. H. Gakiopoulou, P. Korkolopoulou, G. Levidou et al., “Minichromosome maintenance proteins 2 and 5 in non-benign epithelial ovarian tumours: relationship with cell cycle regulators and prognostic implications,” British Journal of Cancer, vol. 97, no. 8, pp. 1124–1134, 2007. View at Publisher · View at Google Scholar · View at Scopus
  105. M. Liu, J.-S. Li, D.-P. Tian, B. Huang, S. Rosqvist, and M. Su, “MCM2 expression levels predict diagnosis and prognosis in gastric cardiac cancer,” Histology and Histopathology, vol. 28, no. 4, pp. 481–492, 2013. View at Google Scholar · View at Scopus
  106. Y. S. Lee, S.-A. Ha, H. J. Kim et al., “Minichromosome maintenance protein 3 is a candidate proliferation marker in papillary thyroid carcinoma,” Experimental and Molecular Pathology, vol. 88, no. 1, pp. 138–142, 2010. View at Publisher · View at Google Scholar · View at Scopus
  107. J. Kikuchi, I. Kinoshita, Y. Shimizu et al., “Minichromosome maintenance (MCM) protein 4 as a marker for proliferation and its clinical and clinicopathological significance in non-small cell lung cancer,” Lung Cancer, vol. 72, no. 2, pp. 229–237, 2011. View at Publisher · View at Google Scholar · View at Scopus
  108. T. J. Dudderidge, J. D. Kelly, A. Wollenschlaeger et al., “Diagnosis of prostate cancer by detection of minichromosome maintenance 5 protein in urine sediments,” The British Journal of Cancer, vol. 103, no. 5, pp. 701–707, 2010. View at Publisher · View at Google Scholar · View at Scopus
  109. T. Zheng, M. Chen, S. Han et al., “Plasma minichromosome maintenance complex component 6 is a novel biomarker for hepatocellular carcinoma patients,” Hepatology Research, 2014. View at Publisher · View at Google Scholar · View at Scopus
  110. K. Nishihara, K. Shomori, S. Fujioka et al., “Minichromosome maintenance protein 7 in colorectal cancer: implication of prognostic significance,” International Journal of Oncology, vol. 33, no. 2, pp. 245–251, 2008. View at Publisher · View at Google Scholar · View at Scopus
  111. S. Fujioka, K. Shomori, K. Nishihara et al., “Expression of minichromosome maintenance 7 (MCM7) in small lung adenocarcinomas (pT1): prognostic implication,” Lung Cancer, vol. 65, no. 2, pp. 223–229, 2009. View at Publisher · View at Google Scholar · View at Scopus
  112. T. Tamura, K. Shomori, T. Haruki et al., “Minichromosome maintenance-7 and geminin are reliable prognostic markers in patients with oral squamous cell carcinoma: Immunohistochemical study,” Journal of Oral Pathology and Medicine, vol. 39, no. 4, pp. 328–334, 2010. View at Publisher · View at Google Scholar · View at Scopus
  113. J. J. Blow and B. Hodgson, “Replication licensing—defining the proliferative state?” Trends in Cell Biology, vol. 12, no. 2, pp. 72–78, 2002. View at Publisher · View at Google Scholar · View at Scopus
  114. J. J. Blow and P. J. Gillespie, “Replication licensing and cancer—a fatal entanglement?” Nature Reviews Cancer, vol. 8, no. 10, pp. 799–806, 2008. View at Publisher · View at Google Scholar · View at Scopus
  115. O. J. Kayes, M. Loddo, N. Patel et al., “DNA replication licensing factors and aneuploidy are linked to tumor cell cycle state and clinical outcome in penile carcinoma,” Clinical Cancer Research, vol. 15, no. 23, pp. 7335–7344, 2009. View at Publisher · View at Google Scholar · View at Scopus
  116. C. P. Harris, X. Y. Lu, G. Narayan, B. Singh, V. V. V. S. Murty, and P. H. Rao, “Comprehensive molecular cytogenetic characterization of cervical cancer cell lines,” Genes Chromosomes and Cancer, vol. 36, no. 3, pp. 233–241, 2003. View at Publisher · View at Google Scholar · View at Scopus
  117. P. H. Rao, H. Arias-Pulido, X.-Y. Lu et al., “Chromosomal amplifications, 3q gain and deletions of 2q33-q37 are the frequent genetic changes incervical carcinoma,” BMC Cancer, vol. 4, article 5, 2004. View at Publisher · View at Google Scholar · View at Scopus
  118. G. Narayan, V. Bourdon, S. Chaganti et al., “Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer: identification of candidate amplified and overexpressed genes,” Genes Chromosomes and Cancer, vol. 46, no. 4, pp. 373–384, 2007. View at Publisher · View at Google Scholar · View at Scopus
  119. T. A. Potapova, J. Zhu, and R. Li, “Aneuploidy and chromosomal instability: a vicious cycle driving cellular evolution and cancer genome chaos,” Cancer and Metastasis Reviews, vol. 32, no. 3-4, pp. 377–389, 2013. View at Publisher · View at Google Scholar · View at Scopus
  120. S. Shreeram, A. Sparks, D. P. Lane, and J. J. Blow, “Cell type-specific responses of human cells to inhibition of replication licensing,” Oncogene, vol. 21, no. 43, pp. 6624–6632, 2002. View at Publisher · View at Google Scholar · View at Scopus
  121. D. Feng, Z. Tu, W. Wu, and C. Liang, “Inhibiting the expression of DNA replication-initiation proteins induces apoptosis in human cancer cells,” Cancer Research, vol. 63, no. 21, pp. 7356–7364, 2003. View at Google Scholar · View at Scopus
  122. Y. Liu, G. He, Y. Wang, X. Guan, X. Pang, and B. Zhang, “MCM-2 is a therapeutic target of Trichostatin A in colon cancer cells,” Toxicology Letters, vol. 221, no. 1, pp. 23–30, 2013. View at Publisher · View at Google Scholar · View at Scopus
  123. E. P. Erkan, T. Ströbel, G. Lewandrowski et al., “Depletion of minichromosome maintenance protein 7 inhibits glioblastoma multiforme tumor growth in vivo,” Oncogene, vol. 33, pp. 4778–4785, 2013. View at Publisher · View at Google Scholar · View at Scopus
  124. T. J. Dudderidge, S. R. McCracken, M. Loddo et al., “Mitogenic growth signalling, DNA replication licensing, and survival are linked in prostate cancer,” British Journal of Cancer, vol. 96, no. 9, pp. 1384–1393, 2007. View at Publisher · View at Google Scholar · View at Scopus
  125. T. Valovka, M. Schönfeld, P. Raffeiner et al., “Transcriptional control of DNA replication licensing by Myc,” Scientific Reports, vol. 3, article 3444, 2013. View at Publisher · View at Google Scholar · View at Scopus
  126. S. Majid, A. A. Dar, S. Saini et al., “Regulation of minichromosome maintenance gene family by MicroRNA-1296 and genistein in prostate cancer,” Cancer Research, vol. 70, no. 7, pp. 2809–2818, 2010. View at Publisher · View at Google Scholar · View at Scopus
  127. J. H. Luo, “Oncogenic activity of MCM7 transforming cluster,” World Journal of Clinical Oncology, vol. 2, no. 2, pp. 120–124, 2011. View at Publisher · View at Google Scholar
  128. K. Yankulov, I. Todorov, P. Romanowski et al., “MCM proteins are associated with RNA polymerase II holoenzyme,” Molecular and Cellular Biology, vol. 19, no. 9, pp. 6154–6163, 1999. View at Google Scholar · View at Scopus
  129. M. Snyder, W. He, and J. J. Zhang, “The DNA replication factor MCM5 is essential for Stat1-mediated transcriptional activation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 41, pp. 14539–14544, 2005. View at Publisher · View at Google Scholar · View at Scopus
  130. M. E. Hubbi, W. Luo, J. H. Baek, and G. L. Semenza, “MCM proteins are negative regulators of hypoxia-inducible factor 1,” Molecular Cell, vol. 42, no. 5, pp. 700–712, 2011. View at Publisher · View at Google Scholar · View at Scopus
  131. I. M. Slaymaker, Y. Fu, D. B. Toso et al., “Mini-chromosome maintenance complexes form a filament to remodel DNA structure and topology,” Nucleic Acids Research, vol. 41, no. 5, pp. 3446–3456, 2013. View at Publisher · View at Google Scholar · View at Scopus