Keywords
MCM2-7 complex; cell proliferation; tumors
How to Cite
MCM2-7 complex: a review. (2019). Odontoestomatología, 20(32), 4-11. https://www.odon.edu.uy/ojs/index.php/ode/article/view/38
Abstract
New cells are formed from preexisting cells through an ordered series of events called cell cycle. As the control of this cycle is fundamental for genome integrity, multiple proteins regulate this process. We currently know that the MCM2-7 complex has a major role in DNA replication in the cell cycle, in particular regarding proliferation. The immunohistochemical identification of the proteins in this complex on tissues may be useful, as they could be used as biomarkers and would help us understand one of the biological mechanisms affected in cancer processes.
Our aim is to collect the existing evidence regarding the members of the MCM2-7 complex, since these proteins could be effective biological cell proliferation markers, which would help practitioners make accurate diagnosis, prognosis and future therapeutic targets of lesions that are mainly neoplastic, especially in the oral mucosa.
References
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6. Arias EE, Walter JC. Strength in numbers: prevent ingress replication via multiple mechanisms in eukaryotic cells. Genes Dev. 2007; 21 (5): 497-518. [ Links ]
7. Alver RC, Chadha GS, Blow JJ. The contribution of dormant origins to genome stability: from cell biology to human genetics. DNA Repair (Amst). 2014; 19: 182-9. [ Links ]
8. Laskey R. The Croonian Lecture 2001 hunting the antisocial cancer cell: MCM proteins and their exploitation. Philos Trans R Soc Lond B Biol Sci. 2005; 360 (1458): 1119-32. [ Links ]
9. Simon NE, Schwacha A. The Mcm2-7 replicative helicase: a promising chemotherapeutic target. Biomed Res Int. 2014; 2014: 549719. doi: 10.1155/2014/549719. [ Links ]
10. 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. [ Links ]
11. 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. [ Links ]
12. Xu M, Chang YP, Chen XS. Expression, purification and biochemical characterization of Schizosaccharomycespombe Mcm4, 6 and 7. BMC Biochem.2013; 14:5. [ Links ]
13. Cortez D, Glick G, Elledge SJ. Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases. Proc Nat lAcad Sci U S A. 2004; 101 (27): 10078-83. [ Links ]
14. Blow JJ, Ge XQ, Jackson DA. How dormant origins promote complete genome replication. Trends Biochem Sci. 2011; 36 (8): 405-14. [ Links ]
15. Tan Z, Wortman M, Dillehay KL, Seibel WL, Evelyn CR, Smith SJ, Malkas LH, Zheng Y, Lu S, Dong Z. Small-molecule targeting of proliferating cell nuclear antigen chromatin association inhibits tumor cell growth. Mol Pharmacol. 2012; 81 (6): 811-9 [ Links ]
16. Bochman ML, Schwacha A. Differences in the single-stranded DNA binding activities of MCM2-7 and MCM467: MCM2 and MCM5 define a slow ATP-dependent step. J Biol Chem. 2007; 282 (46): 33795-804 [ Links ]
17. Bochman ML, Bell SP, Schwacha A. Subunitorganizationof Mcm2-7 and the unequal role of active sites in ATP hydrolysis and viability. Mol Cell Biol. 2008; 28 (19): 5865-73. [ Links ]
18. 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. [ Links ]
19- 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. [ Links ]
20. Das M, Prasad SB, Yadav SS, Govardhan HB, Pandey LK, Singh S, Pradhan S, Narayan G. Over expression of minichromosome maintenance genes is clinically correlated to cervical carcinogenesis. PLoS One. 2013; 8 (7): e69607. [ Links ]
21. Giaginis C, Vgenopoulou S, Vielh P, Theocharis S. MCM proteins as diagnostic and prognostic tumor markers in the clinical setting. Histol Histopathol. 2010; 25 (3): 351-70. [ Links ]
22. Simon NE, Schwacha A. The Mcm2-7 replicative helicase: a promising chemotherapeutic target. Biomed Res Int. 2014; 2014: 549719. doi: 10.1155/2014/549719. [ Links ]
23. Korkolopoulou P, Givalos N, Saetta A, Goudopoulou A, Gakiopoulou H, Thymara I, Thomas-Tsagli E, Patsouris E. Minichromosome maintenance proteins 2 and 5 expression in muscle-invasive urothelial cancer: a multivariate survival study including proliferation markers and cell cycle regulators. Hum Pathol. 2005; 36 (8): 899-907 [ Links ]
24. Gakiopoulou H, Korkolopoulou P, Levidou G, Thymara I, Saetta A, Piperi C, Givalos N, Vassilopoulos I, Ventouri K, Tsenga A, Bamias A, Dimopoulos MA, Agapitos E, Patsouris E. Minichromosome maintenance proteins 2 and 5 in non-benign epithelial ovarian tumours: relationship with cell cycle regulators and prognostic implications. Br J Cancer. 2007; 97 (8): 1124-34. [ Links ]
25. Gouvêa AF, Vargas PA, Coletta RD, Jorge J, Lopes MA. Clinicopathological features and immune histochemical expression of p53, Ki-67, Mcm-2 and Mcm-5 in proliferative verrucous leukoplakia. J Oral Pathol Med. 2010; 39 (6): 447-52. [ Links ]
26. Wharton SB, Chan KK, Anderson JR, Stoeber K, Williams GH. Replicative Mcm2 protein as a novel proliferation marker in oligodendrogliomas and its relationship to Ki67 labelling index, histological grade and prognosis.Neuropathol Appl Neurobiol. 2001; (4): 305-13. [ Links ]
27. Rodins K, Cheale M, Coleman N, Fox SB. Minichromosome maintenance protein 2 expression in normal kidney and renal cell carcinomas: relationship to tumor dormancy and potential clinical utility. Clin Cancer Res. 2002; 8 (4): 1075-81. [ Links ]
28. González MA, Pinder SE, Callagy G, Vowler SL, Morris LS, Pájaro K, Campana JA, Laskey RA, Coleman N. Minichromosome maintenance protein 2 is a Strong independent prognostic marker in breast cancer. J Clin Oncol. 2003; 21 (23): 4306-13. [ Links ]
29. Lee YS, Ha SA, Kim HJ, Shin SM, Kim HK, Kim S, Kang CS, Lee KY, Hong OK, Lee SH, Kwon HS, Cha BY, Kim JW. Minichromosome maintenance protein 3 is a candidate proliferation marker in papillary thyroid carcinoma. Exp Mol Pathol. 2010; 88 (1): 138-42. [ Links ]
30. Kikuchi J, Kinoshita I, Shimizu Y, Kikuchi E, Takeda K, Aburatani H, Oizumi S, Konishi J, Kaga K, Matsuno Y, Birrer MJ, Nishimura M, Dosaka-Akita H. Minichromosome maintenance (MCM) protein 4 as a marker for proliferation and its clinical and clinico pathological significance in non-small cell lung cancer. Lung Cancer. 2011; 72 (2): 229-37. [ Links ]
31. Ladstein RG, Bachmann IM, Straume O, Akslen LA. Ki-67 expression is superior to mitotic count and novel proliferation markers PHH3, MCM4 and mitos in as a prognostic factor in thick cutaneous melanoma. BMC Cancer.2010; 10: 140. [ Links ]
32. 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 (3): 777-85. [ Links ]
33. Liu H, Takeuchi S, Moroi Y, Lin N, Urabe K, Kokuba H, Imafuku S, Dainichi T, Uchi H, Furue M, Tu Y. Expression of mini chromosome maintenance 5 protein in proliferative and malignants kind diseases. Int J Dermatol. 2007; 46 (11): 1171-6. [ Links ]
34. Murphy N, Ring M, Heffron CC, Martin CM, McGuinness E, Sheils O, O'Leary JJ. Quantitation of CDC6 and MCM5 m RNA in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the cervix. Mod Pathol. 2005; 18 (6): 844-9. [ Links ]
35. Yu SY, Wang YP, Chang JY, Shen WR, Chen HM, Chiang CP. Increased expression. of MCM5 is significantly associated with aggressive progression and poor prognosis of oral squamous cell carcinoma. J Oral Pathol Med. 2014; 43 (5): 344-9. [ Links ]
36. Zheng T, Chen M, Han S, Zhang L, Bai Y, Fang X, Ding SZ, Yang Y. Plasma minichromosome maintenance complex componente is a novel biomarker for hepatocellular carcinoma patients. Hepatol Res. 2014; 44 (13): 1347-56. [ Links ]
37. Ren B, Yu G, Tseng GC, Cieply K, Gavel T, Nelson J, Michalopoulos G, Yu YP, Luo JH. MCM7 amplification and over expression are associated with prostate cancer progression. Oncogene. 2006; 25 (7): 1090-8. [ Links ]
38. Nishihara K, Shomori K, Fujioka S, Tokuyasu N, Inaba A, Osaki M, Ogawa T, Ito H. Minichromosome maintenance protein 7 in colo rectal cancer: implication of prognostic significance. Int J Oncol. 2008; 33 (2): 245-51. [ Links ]
39. Fujioka S, Shomori K, Nishihara K, Yamaga K, Nosaka K, Araki K, Haruki T, Taniguchi Y, Nakamura H, Ito H. Expression of minichromosome maintenance 7 (MCM7) in small lung adenocarcinomas (pT1): Prognostic implication. Lung Cancer. 2009; 65 (2): 223-9. [ Links ]
40. Williams GH, Romanowski P, Morris L, Madine M, Mills AD, Stoeber K, Marr J, Laskey RA, Coleman N. Improved cervical smear assessment using antibodies against proteins that regulate DNA replication. Proc Natl Acad Sci U S A. 1998; 95 (25): 14932-7. [ Links ]
41. Stoeber K, Swinn R, Prevost AT, de Clive-Lowe P, Halsall I, Dilworth SM, Marr J, Turner WH, Bullock N, Doble A, Hales CN, Williams GH. Diagnóstico de genito-urinario tracto cáncer mediante la detección de minicromos o mantenimiento 5 de proteínas enorina sedimentos. J Natl Cancer Inst. 2002; 94 (14): 1071-9. [ Links ]
42. Stoeber K, Tlsty TD, Happerfield L, Thomas GA, Romanov S, Bobrow L, Williams ED, Williams GH. DNA replication licensing and human cell proliferation. J Cell Sci. 2001; 114 (Pt 11): 2027-41. [ Links ]
43. Hanna-Morris A, Badvie S, Cohen P, McCullough T, Andreyev HJ, Allen-Mersh TG. Minichromosome maintenance protein 2 (MCM2) is a stronger discriminator of increased proliferation in mucosa adjacent to colorectal cancer than Ki-67. J Clin Pathol. 2009; 62 (4): 325-30 [ Links ]
44. Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000; 182: 311-22. [ Links ]
45. Kodani I, Osaki M, Shomori K, Araki K, Goto E, Ryoke K, Ito H. Minichromosome maintenance 2 expression is correlated with mode of invasion and prognosis in oral squamouscell carcinomas. J Oral PatholMed. 2003: 32 (8): 468-74. [ Links ]
2. Forsburg SL. Eukaryotic MCM proteins: beyond replication initiation. Microbiol Mol Biol Rev. 2004; 68 (1): 109-31. [ Links ]
3. Simon NE, Schwacha A. The Mcm2-7 replicative helicase: a promising chemotherapeutic target. Biomed Res Int. 2014; 2014: 549719. doi: 10.1155/2014/549719. [ Links ]
4. Nguyen V Q, Co C, Irie K, LiJ J. Clb/Cdc28 kinases promote nuclear export of the replication initiator proteins Mcm2-7. Curr. Biol. 2000; 10 (4): 195-205. [ Links ]
5. Braun KA, Breeden LL. Nascent transcription of MCM2-7 is important for nuclear localization of the minichromosome maintenance complex in G1. Mol Biol Cell. 2007; 18 (4): 1447-56. [ Links ]
6. Arias EE, Walter JC. Strength in numbers: prevent ingress replication via multiple mechanisms in eukaryotic cells. Genes Dev. 2007; 21 (5): 497-518. [ Links ]
7. Alver RC, Chadha GS, Blow JJ. The contribution of dormant origins to genome stability: from cell biology to human genetics. DNA Repair (Amst). 2014; 19: 182-9. [ Links ]
8. Laskey R. The Croonian Lecture 2001 hunting the antisocial cancer cell: MCM proteins and their exploitation. Philos Trans R Soc Lond B Biol Sci. 2005; 360 (1458): 1119-32. [ Links ]
9. Simon NE, Schwacha A. The Mcm2-7 replicative helicase: a promising chemotherapeutic target. Biomed Res Int. 2014; 2014: 549719. doi: 10.1155/2014/549719. [ Links ]
10. 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. [ Links ]
11. 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. [ Links ]
12. Xu M, Chang YP, Chen XS. Expression, purification and biochemical characterization of Schizosaccharomycespombe Mcm4, 6 and 7. BMC Biochem.2013; 14:5. [ Links ]
13. Cortez D, Glick G, Elledge SJ. Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases. Proc Nat lAcad Sci U S A. 2004; 101 (27): 10078-83. [ Links ]
14. Blow JJ, Ge XQ, Jackson DA. How dormant origins promote complete genome replication. Trends Biochem Sci. 2011; 36 (8): 405-14. [ Links ]
15. Tan Z, Wortman M, Dillehay KL, Seibel WL, Evelyn CR, Smith SJ, Malkas LH, Zheng Y, Lu S, Dong Z. Small-molecule targeting of proliferating cell nuclear antigen chromatin association inhibits tumor cell growth. Mol Pharmacol. 2012; 81 (6): 811-9 [ Links ]
16. Bochman ML, Schwacha A. Differences in the single-stranded DNA binding activities of MCM2-7 and MCM467: MCM2 and MCM5 define a slow ATP-dependent step. J Biol Chem. 2007; 282 (46): 33795-804 [ Links ]
17. Bochman ML, Bell SP, Schwacha A. Subunitorganizationof Mcm2-7 and the unequal role of active sites in ATP hydrolysis and viability. Mol Cell Biol. 2008; 28 (19): 5865-73. [ Links ]
18. 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. [ Links ]
19- 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. [ Links ]
20. Das M, Prasad SB, Yadav SS, Govardhan HB, Pandey LK, Singh S, Pradhan S, Narayan G. Over expression of minichromosome maintenance genes is clinically correlated to cervical carcinogenesis. PLoS One. 2013; 8 (7): e69607. [ Links ]
21. Giaginis C, Vgenopoulou S, Vielh P, Theocharis S. MCM proteins as diagnostic and prognostic tumor markers in the clinical setting. Histol Histopathol. 2010; 25 (3): 351-70. [ Links ]
22. Simon NE, Schwacha A. The Mcm2-7 replicative helicase: a promising chemotherapeutic target. Biomed Res Int. 2014; 2014: 549719. doi: 10.1155/2014/549719. [ Links ]
23. Korkolopoulou P, Givalos N, Saetta A, Goudopoulou A, Gakiopoulou H, Thymara I, Thomas-Tsagli E, Patsouris E. Minichromosome maintenance proteins 2 and 5 expression in muscle-invasive urothelial cancer: a multivariate survival study including proliferation markers and cell cycle regulators. Hum Pathol. 2005; 36 (8): 899-907 [ Links ]
24. Gakiopoulou H, Korkolopoulou P, Levidou G, Thymara I, Saetta A, Piperi C, Givalos N, Vassilopoulos I, Ventouri K, Tsenga A, Bamias A, Dimopoulos MA, Agapitos E, Patsouris E. Minichromosome maintenance proteins 2 and 5 in non-benign epithelial ovarian tumours: relationship with cell cycle regulators and prognostic implications. Br J Cancer. 2007; 97 (8): 1124-34. [ Links ]
25. Gouvêa AF, Vargas PA, Coletta RD, Jorge J, Lopes MA. Clinicopathological features and immune histochemical expression of p53, Ki-67, Mcm-2 and Mcm-5 in proliferative verrucous leukoplakia. J Oral Pathol Med. 2010; 39 (6): 447-52. [ Links ]
26. Wharton SB, Chan KK, Anderson JR, Stoeber K, Williams GH. Replicative Mcm2 protein as a novel proliferation marker in oligodendrogliomas and its relationship to Ki67 labelling index, histological grade and prognosis.Neuropathol Appl Neurobiol. 2001; (4): 305-13. [ Links ]
27. Rodins K, Cheale M, Coleman N, Fox SB. Minichromosome maintenance protein 2 expression in normal kidney and renal cell carcinomas: relationship to tumor dormancy and potential clinical utility. Clin Cancer Res. 2002; 8 (4): 1075-81. [ Links ]
28. González MA, Pinder SE, Callagy G, Vowler SL, Morris LS, Pájaro K, Campana JA, Laskey RA, Coleman N. Minichromosome maintenance protein 2 is a Strong independent prognostic marker in breast cancer. J Clin Oncol. 2003; 21 (23): 4306-13. [ Links ]
29. Lee YS, Ha SA, Kim HJ, Shin SM, Kim HK, Kim S, Kang CS, Lee KY, Hong OK, Lee SH, Kwon HS, Cha BY, Kim JW. Minichromosome maintenance protein 3 is a candidate proliferation marker in papillary thyroid carcinoma. Exp Mol Pathol. 2010; 88 (1): 138-42. [ Links ]
30. Kikuchi J, Kinoshita I, Shimizu Y, Kikuchi E, Takeda K, Aburatani H, Oizumi S, Konishi J, Kaga K, Matsuno Y, Birrer MJ, Nishimura M, Dosaka-Akita H. Minichromosome maintenance (MCM) protein 4 as a marker for proliferation and its clinical and clinico pathological significance in non-small cell lung cancer. Lung Cancer. 2011; 72 (2): 229-37. [ Links ]
31. Ladstein RG, Bachmann IM, Straume O, Akslen LA. Ki-67 expression is superior to mitotic count and novel proliferation markers PHH3, MCM4 and mitos in as a prognostic factor in thick cutaneous melanoma. BMC Cancer.2010; 10: 140. [ Links ]
32. 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 (3): 777-85. [ Links ]
33. Liu H, Takeuchi S, Moroi Y, Lin N, Urabe K, Kokuba H, Imafuku S, Dainichi T, Uchi H, Furue M, Tu Y. Expression of mini chromosome maintenance 5 protein in proliferative and malignants kind diseases. Int J Dermatol. 2007; 46 (11): 1171-6. [ Links ]
34. Murphy N, Ring M, Heffron CC, Martin CM, McGuinness E, Sheils O, O'Leary JJ. Quantitation of CDC6 and MCM5 m RNA in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the cervix. Mod Pathol. 2005; 18 (6): 844-9. [ Links ]
35. Yu SY, Wang YP, Chang JY, Shen WR, Chen HM, Chiang CP. Increased expression. of MCM5 is significantly associated with aggressive progression and poor prognosis of oral squamous cell carcinoma. J Oral Pathol Med. 2014; 43 (5): 344-9. [ Links ]
36. Zheng T, Chen M, Han S, Zhang L, Bai Y, Fang X, Ding SZ, Yang Y. Plasma minichromosome maintenance complex componente is a novel biomarker for hepatocellular carcinoma patients. Hepatol Res. 2014; 44 (13): 1347-56. [ Links ]
37. Ren B, Yu G, Tseng GC, Cieply K, Gavel T, Nelson J, Michalopoulos G, Yu YP, Luo JH. MCM7 amplification and over expression are associated with prostate cancer progression. Oncogene. 2006; 25 (7): 1090-8. [ Links ]
38. Nishihara K, Shomori K, Fujioka S, Tokuyasu N, Inaba A, Osaki M, Ogawa T, Ito H. Minichromosome maintenance protein 7 in colo rectal cancer: implication of prognostic significance. Int J Oncol. 2008; 33 (2): 245-51. [ Links ]
39. Fujioka S, Shomori K, Nishihara K, Yamaga K, Nosaka K, Araki K, Haruki T, Taniguchi Y, Nakamura H, Ito H. Expression of minichromosome maintenance 7 (MCM7) in small lung adenocarcinomas (pT1): Prognostic implication. Lung Cancer. 2009; 65 (2): 223-9. [ Links ]
40. Williams GH, Romanowski P, Morris L, Madine M, Mills AD, Stoeber K, Marr J, Laskey RA, Coleman N. Improved cervical smear assessment using antibodies against proteins that regulate DNA replication. Proc Natl Acad Sci U S A. 1998; 95 (25): 14932-7. [ Links ]
41. Stoeber K, Swinn R, Prevost AT, de Clive-Lowe P, Halsall I, Dilworth SM, Marr J, Turner WH, Bullock N, Doble A, Hales CN, Williams GH. Diagnóstico de genito-urinario tracto cáncer mediante la detección de minicromos o mantenimiento 5 de proteínas enorina sedimentos. J Natl Cancer Inst. 2002; 94 (14): 1071-9. [ Links ]
42. Stoeber K, Tlsty TD, Happerfield L, Thomas GA, Romanov S, Bobrow L, Williams ED, Williams GH. DNA replication licensing and human cell proliferation. J Cell Sci. 2001; 114 (Pt 11): 2027-41. [ Links ]
43. Hanna-Morris A, Badvie S, Cohen P, McCullough T, Andreyev HJ, Allen-Mersh TG. Minichromosome maintenance protein 2 (MCM2) is a stronger discriminator of increased proliferation in mucosa adjacent to colorectal cancer than Ki-67. J Clin Pathol. 2009; 62 (4): 325-30 [ Links ]
44. Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000; 182: 311-22. [ Links ]
45. Kodani I, Osaki M, Shomori K, Araki K, Goto E, Ryoke K, Ito H. Minichromosome maintenance 2 expression is correlated with mode of invasion and prognosis in oral squamouscell carcinomas. J Oral PatholMed. 2003: 32 (8): 468-74. [ Links ]