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Unwinding Helicase MCM Functionality for Diagnosis and Therapeutics of Replication Abnormalities Associated with Cancer: A Review

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Abstract

The minichromosome maintenance (MCM) protein is a component of an active helicase that is essential for the initiation of DNA replication. Dysregulation of MCM functions contribute to abnormal cell proliferation and genomic instability. The interactions of MCM with cellular factors, including Cdc45 and GINS, determine the formation of active helicase and functioning of helicase. The functioning of MCM determines the fate of DNA replication and, thus, genomic integrity. This complex is upregulated in precancerous cells and can act as an important tool for diagnostic applications. The MCM protein complex can be an important broad-spectrum therapeutic target in various cancers. Investigations have supported the potential and applications of MCM in cancer diagnosis and its therapeutics. In this article, we discuss the physiological roles of MCM and its associated factors in DNA replication and cancer pathogenesis.

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References

  1. Li N, Zhai Y, Zhang Y, Li W, Yang M, Lei J, et al. Structure of the eukaryotic MCM complex at 3.8 Å. Nature. 2015;524(7564):186–91. https://doi.org/10.1038/nature14685.

    Article  CAS  PubMed  Google Scholar 

  2. Maine GT, Sinha P, Tye BK. Mutants of S. cerevisiae defective in the maintenance of minichromosomes. Genetics. 1984;106(3):365–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Moir D, Stewart SE, Osmond BC, Botstein D. Cold-sensitive cell-division-cycle mutants of yeast: isolation, properties, and pseudoreversion studies. Genetics. 1982;100(4):547–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hennessy KM, Botstein D. Regulation of DNA replication during the yeast cell cycle. Cold Spring Harbor Symp Quant Biol. 1991;56:279–84.

    Article  CAS  PubMed  Google Scholar 

  5. Hennessy KM, Lee A, Chen E, Botstein D. A group of interacting yeast DNA replication genes. Genes Dev. 1991;5(6):958–69.

    Article  CAS  PubMed  Google Scholar 

  6. Gibson SI. Analysis of Mcm3, a minichromosome maintenance mutant of yeast with a cell division cycle arrest phenotype. New York: Cornell University; 1989.

    Google Scholar 

  7. Yan H, Gibson S, Tye BK. Mcm2 and Mcm3, two proteins important for ARS activity, are related in structure and function. Genes Dev. 1991;5(6):944–57.

    Article  CAS  PubMed  Google Scholar 

  8. Das M, Singh S, Pradhan S, Narayan G. Mcm paradox: abundance of eukaryotic replicative helicases and genomic integrity. Mol Biol Int. 2014;2014:1–11. https://doi.org/10.1155/2014/574850.

    Article  CAS  Google Scholar 

  9. Schwacha A, Bell SP. Interactions between two catalytically distinct MCM subgroups are essential for coordinated ATP hydrolysis and DNA replication. Mol Cell. 2001;8(5):1093–104. https://doi.org/10.1016/S1097-2765(01)00389-6.

    Article  CAS  PubMed  Google Scholar 

  10. Miller JM, Enemark EJ. Fundamental characteristics of aaa+ protein family structure and function. Archaea. 2016;2016:1–12. https://doi.org/10.1155/2016/9294307.

    Article  CAS  Google Scholar 

  11. Khan YA, White KI, Brunger AT. The aaa+ superfamily: a review of the structural and mechanistic principles of these molecular machines. Crit Rev Biochem Mol Biol. 2021;57(2):156–87. https://doi.org/10.1080/10409238.2021.1979460.

    Article  CAS  PubMed  Google Scholar 

  12. Davey MJ, Indiani C, O’Donnell M. Reconstitution of the Mcm2-7p heterohexamer, subunit arrangement, and ATP site architecture. J Biol Chem. 2003;278(7):4491–9.

    Article  CAS  PubMed  Google Scholar 

  13. 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(6):1433–45.

    Article  CAS  PubMed  Google Scholar 

  14. Kimura H, Ohtomo T, Yamaguchi M, Ishii A, Sugimoto K. Mouse MCM proteins: complex formation and transportation to the nucleus. Genes Cells. 1996;1(11):977–93. https://doi.org/10.1046/j.1365-2443.1996.840284.x.

    Article  CAS  PubMed  Google Scholar 

  15. Krude T, Musahl C, Laskey RA, Knippers R. Human replication proteins hCdc21, hCdc46 and P1Mcm3 bind chromatin uniformly before S-phase and are displaced locally during DNA replication. J Cell Sci. 1996;109(2):309–18.

    Article  CAS  PubMed  Google Scholar 

  16. Romanowski P, Madine MA. Mechanisms restricting DNA replication to once per cell cycle: MCMS, pre-replicative complexes and kinases. Trends Cell Biol. 1996;6(5):184–8. https://doi.org/10.1016/0962-8924(96)10015-5.

    Article  CAS  PubMed  Google Scholar 

  17. Srivastav R, Kumar D, Grover A, Singh A, Manjasetty B, Sharma R, Taneja B. Unique subunit packing in my-cobacterial nanoRNase leads to alternate substrate recognitions in DHH phosphodiesterases. Nucleic Acids Res. 2014;42(12):7894–910.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yang X, Wang C, Nie H, Zhou J, He X, Ou C. Minichromosome maintenance gene family: potential therapeutic targets and prognostic biomarkers for lung squamous cell carcinoma. Aging. 2022;14(22):9167–85. https://doi.org/10.18632/aging.204399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Abid Ali F, Renault L, Gannon J, Gahlon HL, Kotecha A, Zhou JC, et al. Cryo-EM structures of the eukaryotic replicative helicase bound to a translocation substrate. Nat Commun. 2016;7(1):10708. https://doi.org/10.1038/ncomms10708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Dukaj L, Rhind N. The capacity of origins to load MCM establishes replication timing patterns. PLoS Genet. 2021;17(3): e1009467. https://doi.org/10.1371/journal.pgen.1009467.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mehta G, Sanyal K, Abhishek S, Rajakumara E, Ghosh SK. Minichromosome maintenance proteins in eukaryotic chromosome segregation. BioEssays. 2022;44(1):2100218. https://doi.org/10.1002/bies.202100218.

    Article  CAS  Google Scholar 

  22. Fu Y, Lv Z, Kong D, Fan Y, Dong B. High abundance of CDC45 inhibits cell proliferation through elevation of HSPA6. Cell Prolif. 2022;55(7): e13257. https://doi.org/10.1111/cpr.13257.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Dang HQ, Li Z. The Cdc45·Mcm2-7·GINS protein complex in trypanosomes regulates DNA replication and interacts with two Orc1-like proteins in the origin recognition complex. J Biol Chem. 2011;286(37):32424–35. https://doi.org/10.1074/jbc.M111.240143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Petojevic T, Pesavento JJ, Costa A, Liang J, Wang Z, Berger JM, et al. Cdc45 (cell division cycle protein 45) guards the gate of the eukaryote replisome helicase stabilizing leading strand engagement. Proc Natl Acad Sci. 2015. https://doi.org/10.1073/pnas.1422003112.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kang Y, Galal WC, Farina A, Tappin I, Hurwitz J. Properties of the human cdc45/mcm2-7/gins helicase complex and its action with dna polymerase ε in rolling circle dna synthesis. Proc Natl Acad Sci. 2012;109(16):6042–7. https://doi.org/10.1073/pnas.1203734109.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Sun J, Shi R, Zhao S, Li X, Lu S, Bu H, Ma X. Cell division cycle 45 promotes papillary thyroid cancer progression via regulating cell cycle. Tumour Biol J Int Soc Oncodev Biol Med. 2017;39(5):1010428317705342.

    Article  Google Scholar 

  27. Zhang R, Liu Z, Zhang G. CDC45 modulates MCM7 expression and inhibits cell proliferation by suppressing the PI3K/AKT pathway in acute myeloid leukemia. Am J Transl Res. 2021;13(9):10218–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Tanaka S, Araki H. Helicase activation and establishment of replication forks at chromosomal origins of replication. Cold Spring Harb Perspec Biol. 2013;5(12): a010371. https://doi.org/10.1101/cshperspect.a010371.

    Article  CAS  Google Scholar 

  29. Reusswig K, Pfander B. Control of eukaryotic dna replication initiation—mechanisms to ensure smooth transitions. Genes. 2019;10(2):99. https://doi.org/10.3390/genes10020099.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhai Y, Li N, Jiang H, Huang X, Gao N, Tye BK. Unique roles of the non-identical MCM subunits in DNA replication licensing. Mol Cell. 2017;67(2):168–79. https://doi.org/10.1016/j.molcel.2017.06.016.

    Article  CAS  PubMed  Google Scholar 

  31. Chen S, Bell SP. CDK prevents Mcm2–7 helicase loading by inhibiting Cdt1 interaction with Orc6. Genes Dev. 2011;25(4):363–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Tsakraklides V, Bell SP. Dynamics of pre-replicative complex assembly. J Biol Chem. 2010;285(13):9437–43. https://doi.org/10.1074/jbc.m109.072504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Chou H, Bhalla K, Demerdesh OE, Klingbeil O, Hanington K, Aganezov S, et al. The human origin recognition complex is essential for pre-rc assembly, mitosis, and maintenance of nuclear structure. Elife. 2021. https://doi.org/10.7554/elife.61797.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Bochman ML, Schwacha A. The Mcm2-7 complex has in vitro helicase activity. Mol Cell. 2008;31(2):287–93. https://doi.org/10.1016/j.molcel.2008.05.020.

    Article  CAS  PubMed  Google Scholar 

  35. Fei L, Xu H. Role of MCM2–7 protein phosphorylation in human cancer cells. Cell Biosci. 2018;8(1):1–8.

    Article  Google Scholar 

  36. Randell JC, Bowers JL, Rodríguez HK, Bell SP. Sequential ATP hydrolysis by Cdc6 and ORC directs loading of the Mcm2-7 helicase. Mol Cell. 2006;21(1):29–39. https://doi.org/10.1016/j.molcel.2005.11.023.

    Article  CAS  PubMed  Google Scholar 

  37. Pozo PN, Cook JG. Regulation and function of cdt1; a key factor in cell proliferation and genome stability. Genes. 2016;8(1):2. https://doi.org/10.3390/genes801000230.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Li A, Blow JJ. Cdt1 downregulation by proteolysis and geminin inhibition prevents DNA re-replication in Xenopus. EMBO J. 2005;24(2):395–404. https://doi.org/10.1038/sj.emboj.7600520.

    Article  CAS  PubMed  Google Scholar 

  39. Kamimura Y, Tak YS, Sugino A, Araki H. Sld3, which interacts with Cdc45 (Sld4), functions for chro-mosomal DNA replication in Saccharomyces cerevisiae. EMBO J. 2001;20(8):2097–107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Takayama Y, Kamimura Y, Okawa M, Muramatsu S, Sugino A, Araki H. GINS, a novel multiprotein complex required for chromosomal DNA replication in budding yeast. Genes Dev. 2003;17(9):1153–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Bruck I, Pérez-Arnaiz P, Colbert MK, Kaplan DL. Insights into the initiation of eukaryotic DNA replication. Nucleus. 2015;6(6):449–54. https://doi.org/10.1080/19491034.2015.1115938.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Srivastav R, Sharma R, Tandon S, Tandon C. Role of DHH superfamily proteins in nucleic acids metabolism and stress tolerance in prokaryotes and eukaryotes. Int J Biol Macromol. 2019;127:66–75. https://doi.org/10.1016/j.ijbiomac.2018.12.123.

    Article  CAS  PubMed  Google Scholar 

  43. Fu YV, Yardimci H, Long DT, Guainazzi A, Bermudez VP, Hurwitz J, et al. Selective bypass of a lagging strand roadblock by the eukaryotic replicative DNA helicase. Cell. 2011;146(6):931–41. https://doi.org/10.1016/j.cell.2011.07.045.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. 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. https://doi.org/10.1016/j.molcel.2009.12.030.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Sun J, Fernandez-Cid A, Riera A, Tognetti S, Yuan Z, Stillman B, Speck C, Li H. Structural and mechanistic insights into Mcm2-7 double-hexamer assembly and function. Genes Dev. 2014;28(20):2291–303. https://doi.org/10.1101/gad.242313.114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. 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. https://doi.org/10.1038/nature14285.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lõoke M, Maloney MF, Bell SP. Mcm10 regulates DNA replication elongation by stimulating the CMG replicative helicase. Genes Dev. 2017;31(3):291–305.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Dewar JM, Walter JC. Mechanisms of DNA replication termination. Nat Rev Mol Cell Biol. 2017;18(8):507–16. https://doi.org/10.1038/nrm.2017.42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Maric M, Maculins T, De Piccoli G, Labib K. Cdc48 and a ubiquitin ligase drive disassembly of the CMG helicase at the end of DNA replication. Science. 2014;346(6208):1253596. https://doi.org/10.1126/science.1253596.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Priego Moreno S, Bailey R, Campion N, Herron S, Gambus A. Polyubiquitylation drives replisome disassembly at the termination of DNA replication. Science. 2014;346(6208):477–81. https://doi.org/10.1126/science.1253585.

    Article  CAS  Google Scholar 

  51. Katsuki Y, Jeggo PA, Uchihara Y, et al. DNA double-strand break end resection: a critical relay point for determining the pathway of repair and signaling. Genome Instab Dis. 2020;1:155–71. https://doi.org/10.1007/s42764-020-00017-8.

    Article  Google Scholar 

  52. Ali A, Xiao W, Babar ME, Bi Y. Double-stranded break repair in mammalian cells and precise genome editing. Genes. 2022;13(5):737. https://doi.org/10.3390/genes13050737.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Lutzmann M, Bernex F, Jesus CDC, Hodroj D, Marty C, Plo I, et al. Mcm8- and mcm9 deficiencies cause lifelong increased hematopoietic DNA damage driving p53-dependent myeloid tumors. Cell Rep. 2019;28(11):2851–65. https://doi.org/10.1016/j.celrep.2019.07.095.

    Article  CAS  PubMed  Google Scholar 

  54. Li Z, Xu X. Post-translational modifications of the mini-chromosome maintenance proteins in DNA replication. Genes. 2019;10(5):331. https://doi.org/10.3390/genes10050331.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Rubisz P, Hirnle L, Kobierzycki C. The immunohistochemical expression of MCM-3, -5, and -7 proteins in the uterine fibroids. Curr Issues Mol Biol. 2021;43(2):802–17. https://doi.org/10.3390/cimb43020058.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Malumbres M. Cyclin-dependent kinases. Genome Biol. 2014;15(6):1–10. https://doi.org/10.1186/gb4184.

    Article  Google Scholar 

  57. Komamura-Kohno Y, Karasawa-Shimizu K, Saitoh T, Sato M, Hanaoka F, Tanaka S, Ishimi Y. Site-specific phosphorylation of MCM4 during the cell cycle in mammalian cells. FEBS J. 2006;273(6):1224–39. https://doi.org/10.1111/j.1742-4658.2006.05146.x.

    Article  CAS  PubMed  Google Scholar 

  58. Moritani M, Ishimi Y. Inhibition of DNA binding of MCM2-7 complex by phosphorylation with cyclin-dependent kinases. J Biochem. 2013;154(4):363–72.

    Article  CAS  PubMed  Google Scholar 

  59. Cremona CA, Sarangi P, Yang Y, Hang LE, Rahman S, Zhao X. Extensive DNA damage-induced sumoylation contributes to replication and repair and acts in addition to the mec1 checkpoint. Mol Cell. 2012;45(3):422–32. https://doi.org/10.1016/j.molcel.2011.11.028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Golebiowski F, Matic I, Tatham MH, Cole C, Yin Y, Nakamura A, et al. System-wide changes to SUMO modifications in response to heat shock. Sci Signal. 2009. https://doi.org/10.1126/scisignal.2000282.

    Article  PubMed  Google Scholar 

  61. Takei Y, Swietlik M, Tanoue A, Tsujimoto G, Kouzarides T, Laskey R. MCM3AP, a novel acetyltrans-ferase that acetylates replication protein MCM3. EMBO Rep. 2001;2(2):119–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. 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. https://doi.org/10.1093/nar/gkt131.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Madine MA, Swietlik M, Pelizon C, Romanowski P, Mills AD, Laskey RA. The roles of the MCM, ORC, and Cdc6 proteins in determining the replication competence of chromatin in quiescent cells. J Struct Biol. 2000;129(2–3):198–210. https://doi.org/10.1006/jsbi.2000.4218.

    Article  CAS  PubMed  Google Scholar 

  64. Shim YR, Kim A, Gu MJ. Prognostic significance of MCM6 expression in gastrointestinal stromal tumor. Int J Clin Exp Pathol. 2021;14(12):1119–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Yao Y, Dai W. Genomic instability and cancer. J Carcinog Mutagen. 2014;5:1000165. https://doi.org/10.4172/2157-2518.1000165.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Yun HJ, Jeoung DJ, Jin S, Park J, Lee EW, Lee H, et al. Induction of cell cycle arrest, apoptosis, and reducing the expression of mcm proteins in human lung carcinoma a549 cells by cedrol, isolated from juniperus chinensis. J Microbiol Biotechnol. 2022;32(7):918–26. https://doi.org/10.4014/jmb.2205.05012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Wei L, Zhao X. A new MCM modification cycle regulates DNA replication initiation. Nat Struct Mol Biol. 2016;23(3):209–16. https://doi.org/10.1038/nsmb.3173.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Zhou J, Wang M, Zhou Z, Wang W, Duan J, Wu GS. Expression and prognostic value of mcm family genes in osteosarcoma. Front Mol Biosci. 2021. https://doi.org/10.3389/fmolb.2021.668402.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Martinez MP, Wacker AL, Bruck I, Kaplan DL. Eukaryotic replicative helicase subunit interaction with DNA and its role in DNA replication. Genes. 2017;8(4):117. https://doi.org/10.3390/genes8040117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Sun M, Wang T, Zhu Y, Zhang Y, Zhu L, Li X. The high expression of minichromosome maintenance complex component 5 is an adverse prognostic factor in lung adenocarcinoma. BioMed Res Int. 2022. https://doi.org/10.1155/2022/4338793.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Ma H, Liu Z, Li H, Guo X, Guo S, Qu P, Wang Y. Bioinformatics analysis reveals MCM3 as an important prognostic marker in cervical cancer. Comp Math Methods Med. 2021. https://doi.org/10.1155/2021/8494260.

    Article  Google Scholar 

  72. Zhou H, Jiang L, Wang G, Su L, Hou L, Xue X. Identification of MCM4 as a prognostic marker of hepatocellular carcinoma. BioMed Res Int. 2021;2021:1–14.

    Article  Google Scholar 

  73. Meng MV, Grossfeld GD, Williams GH, Dilworth S, Stoeber K, Mulley TW, et al. Mini-chromosome maintenance protein 2 expression in prostate: characterization and association with outcome after therapy for cancer. Clin Cancer Res. 2001;7(9):2712–8.

    CAS  PubMed  Google Scholar 

  74. Nishihara K, Shomori K, Fujioka S, Tokuyasu N, Inaba A, Osaki M, et al. Minichromosome maintenance protein 7 in colorectal cancer: implication of prognostic significance. Int J Oncol. 2008;33(2):245–51. https://doi.org/10.3892/ijo_00000003.

    Article  CAS  PubMed  Google Scholar 

  75. Guzińska-Ustymowicz K, Pryczynicz A, Kemona A, Czyzewska J. Correlation between proliferation markers: PCNA, Ki-67, MCM-2 and antiapoptotic protein Bcl-2 in colorectal cancer. Anticancer Res. 2009;29(8):3049–52.

    PubMed  Google Scholar 

  76. Guzińska-Ustymowicz K, Stepień E, Kemona A. MCM-2, Ki-67 and PCNA protein expressions in pT3G2 colorectal cancer indicated lymph node involvement. Anticancer Res. 2008;28(1B):451–7.

    PubMed  Google Scholar 

  77. Zhong H, Chen B, Neves H, Xing J, Ye Y, Lin Y, et al. Expression of minichromosome maintenance genes in renal cell carcinoma. Cancer Manage Res. 2017;9:637–47.

    Article  CAS  Google Scholar 

  78. Kwok HF, Zhang SD, McCrudden CM, Yuen HF, Ting KP, Wen Q, et al. Prognostic significance of minichromosome maintenance proteins in breast cancer. Am J Cancer Res. 2015;5(1):52.

    PubMed  Google Scholar 

  79. Giaginis C, Giagini A, Tsourouflis G, Gatzidou E, Agapitos E, Kouraklis G, Theocharis S. MCM-2 and MCM-5 expression in gastric adenocarcinoma: clinical significance and comparison with Ki-67 proliferative marker. Dig Dis Sci. 2011;56:777–85. https://doi.org/10.1007/s10620-010-1348-5.

    Article  CAS  PubMed  Google Scholar 

  80. Saydam O, Senol O, Schaaij-Visser TB, Pham TV, Piersma SR, Stemmer-Rachamimov AO, et al. Comparative protein profiling reveals minichromosome maintenance (MCM) proteins as novel potential tumor markers for meningiomas. J Proteome Res. 2010;9(1):485–94. https://doi.org/10.1021/pr900834h.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Yang C, Wen Y, Li H, Zhang D, Zhang N, Shi X, et al. Overexpression of minichromosome maintenance 2 predicts poor prognosis in patients with gastric cancer. Oncol Rep. 2012;27(1):135–42. https://doi.org/10.3892/or.2011.1473.

    Article  CAS  PubMed  Google Scholar 

  82. Xiang S, Reed DR, Alexandrow MG. The CMG helicase and cancer: a tumor “engine” and weakness with missing mutations. Oncogene. 2023;42(7):473–90. https://doi.org/10.1038/s41388-022-02572-8.

    Article  CAS  PubMed  Google Scholar 

  83. Zhang LL, Li Q, Zhong DS, Zhang WJ, Sun XJ, Zhu Y. MCM5 aggravates the HDAC1-mediated malignant progression of lung cancer. Front Cell Dev Biol. 2021;9: 669132. https://doi.org/10.3389/fcell.2021.669132.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Yu S, Wang G, Shi Y, Xu H, Zheng Y, Chen Y. MCMs in Cancer: prognostic potential and mechanisms. Anal Cell Pathol (Amst). 2020;3(2020):3750294.

    Google Scholar 

  85. Symeonidou IE, Kotsantis P, Roukos V, Rapsomaniki MA, Grecco HE, Bastiaens PIH, et al. Multi-step loading of human minichromosome maintenance proteins in live human cells. J Biol Chem. 2013;288(50):35852–67. https://doi.org/10.1074/jbc.m113.474825.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Kuipers MA, Stasevich TJ, Sasaki T, Wilson KA, Hazelwood KL, McNally JG, et al. Highly stable loading of mcm proteins onto chromatin in living cells requires replication to unload. J Cell Biol. 2011;192(1):29–41. https://doi.org/10.1083/jcb.201007111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Gou K, Liu J, Feng X, Li H, Yuan Y, Xing C. Expression of minichromosome maintenance proteins (MCM) and cancer prognosis: a meta-analysis. J Cancer. 2018;9(8):1518–26. https://doi.org/10.7150/jca.22691.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Wang Y, Chen H, Zhang J, Cheng AS, Yu J, To KF, et al. Mcm family in gastrointestinal cancer and other malignancies: from functional characterization to clinical implication. Biochim Biophys Acta. 2020;1874(2): 188415. https://doi.org/10.1016/j.bbcan.2020.188415.

    Article  CAS  Google Scholar 

  89. Wojnar A, Pula B, Piotrowska A, Jethon A, Kujawa K, Kobierzycki C, et al. Correlation of intensity of MT-I/II expression with Ki-67 and MCM-2 proteins in invasive ductal breast carcinoma. Anticancer Res. 2011;31(9):3027–33.

    CAS  PubMed  Google Scholar 

  90. Shima N, Alcaraz A, Liachko I, Buske TR, Andrews CA, Munroe RJ, et al. A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice. Nat Genet. 2007;39(1):93–8. https://doi.org/10.1038/ng1936.

    Article  CAS  PubMed  Google Scholar 

  91. Kaur G, Balasubramaniam SD, Lee YJ, Balakrishnan V, Oon CE. Minichromosome maintenance complex (MCM) genes profiling and MCM2 protein expression in cervical cancer development. Asian Pac J Cancer Prev. 2019;20(10):3043. https://doi.org/10.31557/APJCP.2019.20.10.3043.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Zhou H, Xiong Y, Zhang G, Liu Z, Li L, Hou S, Zhou T. Elevated expression of minichromosome maintenance 3 indicates poor outcomes and promotes G1/S cell cycle progression, proliferation, migration and invasion in colorectal cancer. 2020. Biosci Rep. https://doi.org/10.1042/BSR20201503.

  93. Ha SA, Shin SM, Namkoong H, Lee H, Cho GW, Hur SY, et al. Cancer-associated expression of minichromosome maintenance 3 gene in several human cancers and its involvement in tumorigenesis. Clin Cancer Res. 2004;10(24):8386–95. https://doi.org/10.1158/1078-0432.CCR-04-1029.

    Article  CAS  PubMed  Google Scholar 

  94. Ishimi Y, Okayasu I, Kato C, Kwon HJ, Kimura H, Yamada K, Song SY. Enhanced expression of Mcm proteins in cancer cells derived from uterine cervix. Eur J Biochem. 2003;270(6):1089–101. https://doi.org/10.1046/j.1432-1033.2003.03440.x.

    Article  CAS  PubMed  Google Scholar 

  95. Han J, Lian M, Fang J, Liu H, Wang R, Zhai J, et al. Minichromosome maintenance (MCM) protein 4 overexpression is a potential prognostic marker for laryngeal squamous cell carcinoma. J Buon. 2017;22(5):1272–7.

    PubMed  Google Scholar 

  96. Kikuchi J, Kinoshita I, Shimizu Y, Kikuchi E, Takeda K, Aburatani H, et al. Mini-chromosome maintenance (MCM) protein 4 as a marker for proliferation and its clinical and clinicopathological significance in non-small cell lung cancer. Lung Cancer. 2011;72(2):229–37. https://doi.org/10.1016/j.lungcan.2010.08.020.

    Article  PubMed  Google Scholar 

  97. Xie L, Li T, Yang LH. E2F2 induces MCM4, CCNE2 and WHSC1 upregulation in ovarian cancer and predicts poor overall survival. Eur Rev Med Pharmacol Sci. 2017;21(9):2150–6.

    CAS  PubMed  Google Scholar 

  98. Fei Q, Zou Z, Roundtree IA, Sun H-L, He C. YTHDF2 promotes mitotic entry and is regulated by cell cycle mediators. PLoS Biol. 2020;18(4): e3000664.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Yang Y, Yan Y, Yin J, et al. O-GlcNAcylation of YTHDF2 promotes HBV-related hepatocellular carcinoma progression in an N6-methyladenosine-dependent manner. Sig Transduct Target Ther. 2023;8:63. https://doi.org/10.1038/s41392-023-01316-8.

    Article  CAS  Google Scholar 

  100. Werynska B, Pula B, Muszczynska-Bernhard B, Piotrowska A, Jethon A, Podhorska-Okolow M, et al. Correlation between expression of metallothionein and expression of Ki-67 and MCM-2 proliferation markers in non-small cell lung cancer. Anticancer Res. 2011;31(9):2833–9.

    CAS  PubMed  Google Scholar 

  101. Wang D, Li Q, Li Y, Wang H. The role of MCM5 expression in cervical cancer: correlation with progression and prognosis. Biomed Pharmacother. 2018;98:165–72. https://doi.org/10.1016/j.biopha.2017.12.006.

    Article  CAS  PubMed  Google Scholar 

  102. Issac MSM, Yousef E, Tahir MR, Gaboury LA. MCM2, MCM4, and MCM6 in breast cancer: clinical utility in diagnosis and prognosis. Neoplasia. 2019;21(10):1015–35. https://doi.org/10.1016/j.neo.2019.07.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Liu YZ, Wang BS, Jiang YY, Cao J, Hao JJ, Zhang Y, et al. MCMs expression in lung cancer: implication of prognostic significance. J Cancer. 2017;8(18):3641.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Huang J, Luo HL, Pan H, Qiu C, Hao TF, Zhu ZM. Interaction between RAD51 and MCM complex is essential for RAD51 foci forming in colon. Biochemistry (Mosc). 2018;83(1):69–75.

    Article  CAS  PubMed  Google Scholar 

  105. Zhong X, Chen X, Guan X, Zhang H, Ma Y, Zhang S, et al. Overexpression of G 9a and MCM 7 in oesophageal squamous cell carcinoma is associated with poor prognosis. Histopathology. 2015;66(2):192–200. https://doi.org/10.1111/his.12456.

    Article  PubMed  Google Scholar 

  106. Kobierzycki C, Pula B, Skiba M, Jablonska K, Latkowski K, Zabel M, et al. Comparison of minichromosome maintenance proteins (MCM-3, MCM-7) and metallothioneins (MT-I/II, MT-III) expression in relation to clinicopathological data in ovarian cancer. Anticancer Res. 2013;33(12):5375–83.

    CAS  PubMed  Google Scholar 

  107. Hua C, Zhao G, Li Y, Bie L. Minichromosome maintenance (MCM) family as potential diagnostic and prognostic tumor markers for human gliomas. BMC Cancer. 2014;14(1):1–8. https://doi.org/10.1186/1471-2407-14-526.

    Article  CAS  Google Scholar 

  108. Padmanabhan V, Callas P, Philips G, Trainer TD, Beatty BG. DNA replication regulation protein Mcm7 as a marker of proliferation in prostate cancer. J Clin Pathol. 2004;57(10):1057–62. https://doi.org/10.1136/jcp.2004.016436.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Peng YP, Zhu Y, Yin LD, Zhang JJ, Guo S, Fu Y, et al. The expression and prognostic roles of MCMs in pancreatic cancer. PLoS ONE. 2016;11(10): e0164150.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Helderman NC, Terlouw D, Bonjoch L, Golubicki M, Antelo M, Morreau H, et al. Molecular functions of MCM8 and MCM9 and their associated pathologies. Science. 2023;26(6):106737. https://doi.org/10.1016/j.isci.2023.106737.

    Article  CAS  Google Scholar 

  111. Cui F, Hu J, Ning S, Tan J, Tang H. Overexpression of MCM10 promotes cell proliferation and predicts poor prognosis in prostate cancer. Prostate. 2018;78(16):1299–310. https://doi.org/10.1002/pros.23703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Chen D, Zhong N, Guo Z, Ji Q, Dong Z, Zheng J, Ma Y, Zhang J, He Y, Song T. MCM10, a potential diagnostic, immunological, and prognostic biomarker in pan-cancer. Sci Rep. 2023;13(1):17701. https://doi.org/10.1038/s41598-023-44946-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Wang L, Liu X. Pan-Cancer Multi-Omics Analysis of Minichromosome Maintenance Proteins (MCMs) Expression in Human Cancers. Front Biosci (Landmark Ed). 2023;28(9):230. https://doi.org/10.31083/j.fbl2809230.

    Article  PubMed  Google Scholar 

  114. Lee WL, Huang JY, Shyur LF. Phytoagents for cancer management: regulation of nucleic acid oxidation, ROS, and related mechanisms. Oxid Med Cell Longev. 2013. https://doi.org/10.1155/2013/925804.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Yan X-B, Xie T, Wang SD, Wang Z, Li HY, Ye ZM. Apigenin inhibits proliferation of human chon-drosarcoma cells via cell cycle arrest and mitochondrial apoptosis induced by ROS generation-an in vitro and in vivo study. Int J Clin Exp Med. 2018;11(3):1615–31.

    Google Scholar 

  116. Lu L, Zhao Z, Liu L, Gong W, Dong J. Combination of baicalein and docetaxel additively inhibits the growth of non-small cell lung cancer in vivo. Trad Med Mod Med. 2018;1(03):213–8. https://doi.org/10.1142/S2575900018500131.

    Article  Google Scholar 

  117. Seo YS, Kang YH. The human replicative helicase, the CMG complex, as a target for anti-cancer therapy. Front Mol Biosci. 2018;5:26. https://doi.org/10.3389/fmolb.2018.00026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Choudhari AS, Mandave PC, Deshpande M, Ranjekar P, Prakash O. Phytochemicals in cancer treatment: From preclinical studies to clinical practice. Front Pharmacol. 2020;10:1614. https://doi.org/10.3389/fphar.2019.01614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Yin M, Baslan T, Walker RL, Zhu YJ, Freeland A, Matsukawa T, Sridharan S, Nussenzweig A, Pruitt SC, Lowe SW, Meltzer PS, Aplan PD. A unique mutator phenotype reveals complementary oncogenic lesions leading to acute leukemia. JCI Insight. 2019;4(23): e131434. https://doi.org/10.1172/jci.insight.131434.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Rusiniak ME, Kunnev D, Freeland A, Cady GK, Pruitt SC. Mcm2 deficiency results in short deletions allowing high resolution identification of genes contributing to lymphoblastic lymphoma. Oncogene. 2012;31(36):4034–44. https://doi.org/10.1038/onc.2011.566.

    Article  CAS  PubMed  Google Scholar 

  121. Gineau L, Cognet C, Kara N, Lach FP, Dunne J, Veturi U, Picard C, Trouillet C, Eidenschenk C, Aoufouchi S, Alcaïs A, Smith O, Geissmann F, Feighery C, Abel L, Smogorzewska A, Stillman B, Vivier E, Casanova JL, Jouanguy E. Partial MCM4 deficiency in patients with growth retardation, adrenal insufficiency, and natural killer cell deficiency. J Clin Invest. 2012;122(3):821–32. https://doi.org/10.1172/JCI61014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Liu Y, He G, Wang Y, Guan X, Pang X, Zhang B. MCM-2 is a therapeutic target of trichostatin A in colon cancer cells. Toxicol Lett. 2013;221(1):23–30. https://doi.org/10.1016/j.toxlet.2013.05.643.

    Article  CAS  PubMed  Google Scholar 

  123. Hsu EC, Shen M, Aslan M, et al. MCM2-7 complex is a novel druggable target for neuroendocrine prostate cancer. Sci Rep. 2021;11:13305. https://doi.org/10.1038/s41598-021-92552-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Greiwe JF, Miller TL, Locke J, Martino F, Howell S, Schreiber A, et al. Structural mechanism for the selective phosphorylation of dna-loaded mcm double hexamers by the dbf4-dependent kinase. Nat Mol Biol. 2021;29(1):10–20. https://doi.org/10.1038/s41594-021-00698-z.

    Article  CAS  Google Scholar 

  125. Mulvaney KM, Matson JP, Siesser PF, Tamir TY, Goldfarb D, Jacobs TM, et al. Identification and characterization of mcm3 as a kelch-like ech-associated protein 1 (keap1) substrate. J Biol Chem. 2016;291(45):23719–33. https://doi.org/10.1074/jbc.m116.729418.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Dou J, Wang Z, Ma L, Peng B, Mao K, Li C, et al. Baicalein and baicalin inhibit colon cancer using two distinct fashions of apoptosis and senescence. Oncotarget. 2018;9(28):20089.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Hong YK, Oh YN, Hyun SK, Yun HJ, Hwang HJ, Lee EW, et al. Widdrol induces cell cycle arrest and MCM down expression in human lung carcinoma cells. Cancer Lett. 2009;290:96–103.

    PubMed  Google Scholar 

  128. Kwon HJ, Hong YK, Park C, Choi YH, Yun HJ, Lee EW, Kim BW. Widdrol induces cell cycle arrest, associated with MCM down-regulation, in human colon adenocarcinoma cells. Cancer Lett. 2010;290(1):96–103. https://doi.org/10.1016/j.canlet.2009.09.003.

    Article  CAS  PubMed  Google Scholar 

  129. Yun HJ, Hyun SK, Park JH, Kim BW, Kwon HJ. Widdrol activates DNA damage checkpoint through the signaling Chk2-p53- Cdc25A-p21-MCM4 pathway in HT29 cells. Mol Cell Biochem. 2012;363:281–9. https://doi.org/10.1007/s11010-011-1180-z.

    Article  CAS  PubMed  Google Scholar 

  130. Shaikh SB, Najar MA, Prasad TSK, Bhandary YP. Comparative protein profiling reveals the inhibitory role of curcumin on il-17a mediated minichromosome maintenance (mcm) proteins as novel putative markers for acute lung injury in vivo. Biomed Pharmacother. 2021;141: 111715. https://doi.org/10.1016/j.biopha.2021.111715).

    Article  CAS  PubMed  Google Scholar 

  131. Andalib KS, Biswas P, Sakib MR, Hasan MN, Rahman H, Habib A. Identification of novel mcm2 inhibitors from catharanthus roseus by pharmacoinformatics, molecular docking and molecular dynamics simulation-based evaluation. Inf Med Unlocked. 2023;39: 101251. https://doi.org/10.1016/j.imu.2023.101251.

    Article  Google Scholar 

  132. Alshahrani MY, Alshahrani KM, Tasleem M, Akeel A, Almeleebia TM, Ahmad I, et al. Computational screening of natural compounds for identification of potential anti-cancer agents targeting MCM7 protein. Molecules. 2021;26(19):5878. https://doi.org/10.3390/molecules26195878.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Geng Y, Chen S, Yang Y, Miao H, Li X, Li G, Liu Y. Long-term exposure to genistein inhibits the proliferation of gallbladder cancer by downregulating the MCM complex. Sci Bull. 2022;67(8):813–24. https://doi.org/10.1016/j.scib.2022.01.011.

    Article  CAS  Google Scholar 

  134. Parvizpour S, Masoudi-Sobhanzadeh Y, Pourseif MM, Barzegari A, Razmara J, Omidi Y. Pharma-coinformatics-based phytochemical screening for anticancer impacts of yellow sweet clover, Melilotus officinalis (Linn.) Pall. Comp Biol Med. 2021;138:104921. https://doi.org/10.1016/j.compbiomed.2021.104921.

    Article  CAS  Google Scholar 

  135. Guan YB, Yang DR, Nong SJ, Ni J, Hu CH, Li J, Zhu J, Shan YX. Breviscapine (BVP) inhibits prostate cancer progression through damaging DNA by minichromosome maintenance protein-7 (MCM-7) modulation. Biomed Pharmacother. 2017;1(93):103–16.

    Article  Google Scholar 

  136. Majid S, Dar AA, Saini S, Chen Y, Shahryari V, Liu J, et al. Regulation of minichromosome maintenance gene family by microRNA-1296 and genistein in prostate cancer regulation of mcm gene family in prostate cancer. Cancer Res. 2010;70(7):2809–18.

    Article  CAS  PubMed  Google Scholar 

  137. Ilves I, Tamberg N, Botchan MR. Checkpoint kinase 2 (Chk2) inhibits the activity of the Cdc45/MCM2-7/GINS (CMG) replicative helicase complex. Proc Natl Acad Sci. 2012;109(33):13163–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Jin SF, Ma HL, Liu ZL, Fu ST, Zhang CP, He Y. XL413, a cell division cycle 7 kinase inhibitor enhanced the anti-fibrotic effect of pirfenidone on TGF-β1-stimulated C3H10T1/2 cells via Smad2/4. Exper Cell Res. 2015;339(2):289–99.

    Article  CAS  Google Scholar 

  139. Yang S, Ren X, Liang Y, Yan Y, Zhou Y, Hu J, Wang Z, Song F, Wang F, Liao W, Liao W. KNK437 restricts the growth and metastasis of colorectal cancer via targeting DNAJA1/CDC45 axis. Oncogene. 2020;39(2):249–61.

    Article  CAS  PubMed  Google Scholar 

  140. Nepon-Sixt BS, Alexandrow MG. TGFβ1 cell cycle arrest is mediated by inhibition of MCM assembly in Rb-deficient conditions. Mol Cancer Res. 2019;17(1):277–88.

    Article  PubMed  Google Scholar 

  141. Pauzaite T, Tollitt J, Sopaci B, Caprani L, Iwanowytsch O, Thacker U, Hardy JG, Allinson SL, Copeland NA. Dbf4-Cdc7 (DDK) inhibitor PHA-767491 displays potent anti-proliferative effects via crosstalk with the CDK2-RB-E2F pathway. Biomedicines. 2022;10(8):2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Schwacha A, Seibel WL, Brodsky JL, Seguin S, Bochman ML, Simon N. Ciprofloxacin is an inhibitor of the Mcm2-7 replicative helicase. Biosci Rep. 2013;33(5): e000072.

    Google Scholar 

  143. Caillat C, Perrakis A. Cdt1 and geminin in DNA replication initiation. Subcell Biochem. 2012;62:71–87.

    Article  CAS  PubMed  Google Scholar 

  144. Numata Y, Ishihara S, Hasegawa N, Nozaki N, Ishimi Y. Interaction of human MCM2-7 proteins with TIM, TIPIN and Rb. J Biochem. 2010;147(6):917–27.

    Article  CAS  PubMed  Google Scholar 

  145. Ishimi Y, Sugiyama T, Nakaya R, Kanamori M, Kohno T, Enomoto T, Chino M. Effect of heliquinomycin on the activity of human minichromosome maintenance 4/6/7 helicase. FEBS J. 2009;276(12):3382–91.

    Article  CAS  PubMed  Google Scholar 

  146. Rizwani W, Alexandrow MG, Chellappan SP. Prohibitin physically interacts with MCM proteins and inhibits mammalian DNA replication. Cell Cycle. 2009;8(10):1621–9.

    Article  CAS  PubMed  Google Scholar 

  147. Braden WA, Lenihan JM, Lan Z, Luce KS, Zagorski W, Bosco E, Reed MF, Cook JG, Knudsen ES. Distinct action of the retinoblastoma pathway on the DNA replication machinery defines specific roles for cyclin-dependent kinase complexes in prereplication complex assembly and S-phase progression. Mol Cell Biol. 2006;26(20):7667–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Zhang X, Teng Y, Yang F, Wang M, Hong X, Ye LG, Gao YN, Chen GY. MCM2 is a therapeutic target of lovastatin in human non-small cell lung carcinomas. Oncol Rep. 2015;33(5):2599–605.

    Article  CAS  PubMed  Google Scholar 

  149. Bellelli R, Castellone MD, Guida T, Limongello R, Dathan NA, Merolla F, Cirafici AM, Affuso A, Masai H, Costanzo V, Grieco D, Fusco A, Santoro M, Carlomagno F. NCOA4 transcriptional coactivator inhibits activation of DNA replication origins. Mol Cell. 2014;55(1):123–37. https://doi.org/10.1016/j.molcel.2014.04.031. (Epub 2014 Jun 5 PMID: 24910095).

    Article  CAS  PubMed  Google Scholar 

  150. Grover R, Burse S, Shankrit S, Aggarwal A, Kirty K, Narta K, Srivastav R, Ray AK, Malik G, Vats A, Motiani RK, Thukral L, Roy SS, Bhattacharya S, Sharma R, Natarajan K, Mukerji M, Pandey R, Gokhale RS, Natarajan VT. Myg1 exonuclease couples the nuclear and mitochondrial translational programs through RNA processing. Nucleic Acids Res. 2019;47(11):5852–66. https://doi.org/10.1093/nar/gkz371.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Mahadevappa R, Neves H, Yuen SM, Jameel M, Bai Y, Yuen HF, et al. DNA replication licensing protein MCM10 promotes tumor progression and is a novel prognostic biomarker and potential therapeutic target in breast cancer. Cancers. 2018;10(9):282. https://doi.org/10.3390/cancers10090282.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Scapulatempo-Neto C, Veo C, Fregnani J, Lorenzi A, Mafra A, Melani AGF, et al. Characterization of topoisomerase II alpha and minichromosome maintenance protein 2 expression in anal carcinoma. Oncol Lett. 2017;13:1891–8. https://doi.org/10.3892/ol.2017.5650.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Tokuyasu N, Shomori K, Nishihara K, Kawaguchi H, Fujioka S, Yamaga K, et al. Minichromosome maintenance 2 (MCM2) immunoreactivity in stage III human gastric carcinoma: clinicopathological significance. Gastric Cancer. 2008;11:37–46. https://doi.org/10.1007/s10120-008-0451-1.

    Article  CAS  PubMed  Google Scholar 

  154. Gambichler T, Breininger A, Rotterdam S, Altmeyer P, Stucker M, Kreuter A. Expression of minichromosome maintenance proteins in Merkel cell carcinoma. J Eur Acad Dermatol Venereol. 2009;23:1184–8. https://doi.org/10.1111/j.1468-3083.2009.03285.x.

    Article  CAS  PubMed  Google Scholar 

  155. Razavi SM, Jafari M, Heidarpoor M, Khalesi S. Minichromosome maintenance-2 (MCM2) expression differentiates oral squamous cell carcinoma from pre-cancerous lesions. Malays J Pathol. 2015;37:253–8.

    PubMed  Google Scholar 

  156. Abe N, Matsuo K, Kumasaka T, Naka K, Hashimoto S, Takemura T, et al. Systematic cytological evaluation and immunocytochemistry of minichromosome maintenance protein 2 and p53 significantly improve cytological diagnosis of pancreaticobiliary adenocarcinoma. J Med Dent Sci. 2016;63:19–27. https://doi.org/10.11480/jmds.630103.

    Article  PubMed  Google Scholar 

  157. Vargas PA, Cheng Y, Barrett AW, Craig GT, Speight PM. Expression of Mcm-2, Ki-67 and geminin in benign and malignant salivary gland tumours. J Oral Pathol Med. 2008;37:309–18. https://doi.org/10.1111/j.1600-0714.2007.00631.x.

    Article  CAS  PubMed  Google Scholar 

  158. Schimmack S, Lawrence B, Kenney B, Schmitz-Winnenthal H, Modlin IM, Kidd M. Minichromosome maintenance expression defines slowgrowing gastroenteropancreatic neuroendocrine neoplasms. Transl Oncol. 2016;9:411–8. https://doi.org/10.1016/j.tranon.2016.07.006.

    Article  PubMed  PubMed Central  Google Scholar 

  159. Igci YZ, Erkilic S, Igci M, Arslan A. MCM3 protein expression in follicular and classical variants of papillary thyroid carcinoma. Pathol Oncol Res. 2014;20:87–91. https://doi.org/10.1007/s12253-013-9662-9.

    Article  CAS  PubMed  Google Scholar 

  160. Zielinski R, Kobos J, Zakrzewska A. Comparison between immunohistochemical expression of Ki-67 and MCM-3 in major salivary gland epithelial tumors in children and adolescents. Preliminary study. Pol J Pathol. 2016;67:351–6. https://doi.org/10.5114/pjp.2016.65868.

    Article  PubMed  Google Scholar 

  161. Huang TH, Huo L, Wang YN, Xia W, Wei Y, Chang SS, et al. Epidermal growth factor receptor potentiates MCM7-mediated DNA replication through tyrosine phosphorylation of Lyn kinase in human cancers. Cancer Cell. 2013;23:796–810. https://doi.org/10.1016/j.ccr.2013.04.027.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Choy B, LaLonde A, Que J, Wu T, Zhou Z. MCM4 and MCM7, potential novel proliferation markers, significantly correlated with Ki-67, Bmi1, and cyclin E expression in esophageal adenocarcinoma, squamous cell carcinoma, and precancerous lesions. Hum Pathol. 2016;57:126–35. https://doi.org/10.1016/j.humpath.2016.07.013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Dudderidge TJ, Kelly JD, Wollenschlaeger A, Okoturo O, Prevost T, Robson W, et al. Diagnosis of prostate cancer by detection of minichromosome maintenance 5 protein in urine sediments. Br J Cancer. 2010;103:701–7. https://doi.org/10.1038/sj.bjc.6605785.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Henderson D, Hall L, Prpic N, Hessling J, Parker M, Sampson S, et al. The selection and characterization of antibodies to minichromosome maintenance proteins that highlight cervical dysplasia. J Immunol Methods. 2011;370:1–13. https://doi.org/10.1016/j.jim.2011.04.008.

    Article  CAS  PubMed  Google Scholar 

  165. Lee JS, Cheong HS, Koh Y, Ahn KS, Shin HD, Yoon SS. MCM7 polymorphisms associated with the AML relapse and overall survival. Ann Hematol. 2017;96:93–8. https://doi.org/10.1007/s00277-016-2844-2.

    Article  CAS  PubMed  Google Scholar 

  166. Kimura F, Kawamura J, Watanabe J, Kamoshida S, Kawai K, Okayasy I, et al. Significance of cell proliferation markers (Minichromosome maintenance protein 7, topoisomerase IIα and Ki-67) in cavital fluid cytology: can we differentiate reactive mesothelial cells from malignant cells? Diagn Cytopathol. 2009;38:161–7. https://doi.org/10.1002/dc.21190.

    Article  Google Scholar 

  167. Kimura F, Okayasu I, Kakinuma H, Satoh Y, Kuwao S, Saegusa M, et al. Differential diagnosis of reactive mesothelial cells and malignant mesothelioma cells using the cell proliferation markers minichromosome maintenance protein 7, geminin, topoisomerase II alpha and Ki-67. Acta Cytol. 2013;57:384–90. https://doi.org/10.1159/000350262.

    Article  CAS  PubMed  Google Scholar 

  168. Tamura T, Shomori K, Haruki T, Nosaka K, Hamamoto Y, Shiomi T, et al. Minichromosome maintenance-7 and geminin are reliable prognostic markers in patients with oral squamous cell carcinoma: immunohistochemical study. J Oral Pathol Med. 2010;39:328–34. https://doi.org/10.1111/j.1600-0714.2009.00861.x.

    Article  CAS  PubMed  Google Scholar 

  169. Shohet JM, Hicks MJ, Plon SE, Burlingame SM, Stuart S, Chen SY, et al. Minichromosome maintenance protein MCM7 is a direct target of the MYCN transcription factor in neuroblastoma. Cancer Res. 2002;62:1123–8.

    CAS  PubMed  Google Scholar 

  170. Sun Y, Cheng Z, Liu S. MCM2 in human cancer: functions, mechanisms, and clinical significance. Mol Med. 2022;28:128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

A.R. and R.S. and acknowledge INSPIRE-Department of Science and Technology, Ministry of Science and Technology, New Delhi, India for INSPIRE faculty fellowship (IFA16LSBM184) during the work. R.S. acknowledges Dr. Girish Sharma, Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida for guidance and support during manuscript preparation. R.S. is thankful to Prof. Rakesh Sharma, Senior Principal Scientist, CSIR-Institute of Genomics and Integrative Biology for the support and guidance during the work.

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Conflicts of Interest

All authors, Arathi Radhakrishnan, Ritwik Gangopadhyay, Dr. Chandresh Sharma, Dr. Raj Kishor Kapardar, Dr. Nilesh Kumar Sharma, Dr. Rajpal Srivastav, declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Ms. Arathi Radhakrishnan: methodology, writing—review and editing, and resources. Mr. Ritwik Gangopadhyay: methodology and resources. Dr. Chandresh Sharma: methodology and resources. Dr. Raj Kishor Kapardar: methodology and resources. Dr. Nilesh Sharma: formal analysis, investigation and methodology. Dr. Rajpal Srivastav: conceptualization, investigation, methodology, resources, validation, and writing—original draft, review, and editing.

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Radhakrishnan, A., Gangopadhyay, R., Sharma, C. et al. Unwinding Helicase MCM Functionality for Diagnosis and Therapeutics of Replication Abnormalities Associated with Cancer: A Review. Mol Diagn Ther (2024). https://doi.org/10.1007/s40291-024-00701-5

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