Top

06-09-2024 | REVIEW

Multifaceted role of the DNA replication protein MCM10 in maintaining genome stability and its implication in human diseases

Authors: Sumayyah M. Q. Ahmed, Jayaprakash Sasikumar, Suparna Laha, Shankar Prasad Das

Published in: Cancer and Metastasis Reviews

Abstract

MCM10 plays a vital role in genome duplication and is crucial for DNA replication initiation, elongation, and termination. It coordinates several proteins to assemble at the fork, form a functional replisome, trigger origin unwinding, and stabilize the replication bubble. MCM10 overexpression is associated with increased aggressiveness in breast, cervical, and several other cancers. Disruption of MCM10 leads to altered replication timing associated with initiation site gains and losses accompanied by genome instability. Knockdown of MCM10 affects the proliferation and migration of cancer cells, manifested by DNA damage and replication fork arrest, and has recently been shown to be associated with clinical conditions like CNKD and RCM. Loss of MCM10 function is associated with impaired telomerase activity, leading to the accumulation of abnormal replication forks and compromised telomere length. MCM10 interacts with histones, aids in nucleosome assembly, binds BRCA2 to maintain genome integrity during DNA damage, prevents lesion skipping, and inhibits PRIMPOL-mediated repriming. It also interacts with the fork reversal enzyme SMARCAL1 and inhibits fork regression. Additionally, MCM10 undergoes several post-translational modifications and contributes to transcriptional silencing by interacting with the SIR proteins. This review explores the mechanism associated with MCM10’s multifaceted role in DNA replication initiation, chromatin organization, transcriptional silencing, replication stress, fork stability, telomere length maintenance, and DNA damage response. Finally, we discuss the role of MCM10 in the early detection of cancer, its prognostic significance, and its potential use in therapeutics for cancer treatment.

Sclafani, R. A., & Holzen, T. M. (2007). Cell cycle regulation of DNA replication. Annual Review of Genetics, 41, 237–280. https://doi.org/10.1146/annurev.genet.41.110306.130308CrossRefPubMedPubMedCentral

DePamphilis, M. L. (2016). Genome duplication: The heartbeat of developing organisms. Current Topics in Developmental Biology, 116, 201–229. https://doi.org/10.1016/bs.ctdb.2015.10.002CrossRefPubMedPubMedCentral

Gaillard, H., García-Muse, T., & Aguilera, A. (2015). Replication stress and cancer. Nature Reviews Cancer, 15, 276–289. https://doi.org/10.1038/nrc3916CrossRefPubMed

Waterman, D. P., Haber, J. E., & Smolka, M. B. (2020). Checkpoint responses to DNA double-strand breaks. Annual Review of Biochemistry, 89, 103–133. https://doi.org/10.1146/annurev-biochem-011520-104722CrossRefPubMedPubMedCentral

Mughal, M. J., Chan, K. I., Mahadevappa, R., Wong, S. W., Wai, K. C., & Kwok, H. F. (2022). Over-Activation of Minichromosome Maintenance Protein 10 Promotes Genomic Instability in Early Stages of Breast Cancer. International Journal of Biological Sciences, 18, 3827–3844. https://doi.org/10.7150/ijbs.69344CrossRefPubMedPubMedCentral

Bell, S. P. (2017). Rethinking origin licensing. eLife, 6, e24052. https://doi.org/10.7554/eLife.24052CrossRefPubMedPubMedCentral

Lewis, J. S., Gross, M. H., Sousa, J., Henrikus, S. S., Greiwe, J. F., Nans, A., Diffley, J. F. X., & Costa, A. (2022). Mechanism of replication origin melting nucleated by CMG helicase assembly. Nature, 606, 1007–1014. https://doi.org/10.1038/s41586-022-04829-4CrossRefPubMedPubMedCentral

Polasek-Sedlackova, H., Miller, T. C. R., Krejci, J., Rask, M.-B., & Lukas, J. (2022). Solving the MCM paradox by visualizing the scaffold of CMG helicase at active replisomes. Nature Communications, 13, 6090. https://doi.org/10.1038/s41467-022-33887-5CrossRefPubMedPubMedCentral

Wang, Y., Chen, H., Zhang, J., Cheng, A. S. L., Yu, J., To, K. F., & Kang, W. (2020). MCM family in gastrointestinal cancer and other malignancies: From functional characterization to clinical implication. Biochimica et Biophysica Acta - Reviews on Cancer, 1874, 188415. https://doi.org/10.1016/j.bbcan.2020.188415CrossRefPubMed

10.

Briu, L.-M., Maric, C., & Cadoret, J.-C. (2021). Replication Stress, Genomic Instability, and Replication Timing: A Complex Relationship. International Journal of Molecular Sciences, 22, 4764. https://doi.org/10.3390/ijms22094764CrossRefPubMedPubMedCentral

11.

Warren, E. M., Huang, H., Fanning, E., Chazin, W. J., & Eichman, B. F. (2009). Physical Interactions between Mcm10, DNA, and DNA Polymerase α *. Journal of Biological Chemistry, 284, 24662–24672. https://doi.org/10.1074/jbc.M109.020438CrossRefPubMedPubMedCentral

12.

Kanke, M., Kodama, Y., Takahashi, T. S., Nakagawa, T., & Masukata, H. (2012). Mcm10 plays an essential role in origin DNA unwinding after loading of the CMG components. EMBO Journal, 31, 2182–2194. https://doi.org/10.1038/emboj.2012.68CrossRefPubMedPubMedCentral

13.

Solomon, N. A., Wright, M. B., Chang, S., Buckley, A. M., Dumas, L. B., & Gaber, R. F. (1992). Genetic and molecular analysis of DNA43 and DNA52: Two new cell-cycle genes in Saccharomyces cerevisiae. Yeast Chichester Engl., 8, 273–289. https://doi.org/10.1002/yea.320080405CrossRef

14.

Merchant, A. M., Kawasaki, Y., Chen, Y., Lei, M., & Tye, B. K. (1997). A lesion in the DNA replication initiation factor Mcm10 induces pausing of elongation forks through chromosomal replication origins in Saccharomyces cerevisiae. Molecular and Cellular Biology, 17, 3261–3271.CrossRefPubMedPubMedCentral

15.

Wohlschlegel, J. A., Dhar, S. K., Prokhorova, T. A., Dutta, A., & Walter, J. C. (2002). Xenopus Mcm10 binds to origins of DNA replication after Mcm2-7 and stimulates origin binding of Cdc45. Molecular Cell, 9, 233–240. https://doi.org/10.1016/s1097-2765(02)00456-2CrossRefPubMed

16.

Gregan, J., Lindner, K., Brimage, L., Franklin, R., Namdar, M., Hart, E. A., Aves, S. J., & Kearsey, S. E. (2003). Fission yeast Cdc23/Mcm10 functions after pre-replicative complex formation to promote Cdc45 chromatin binding. Molecular Biology of the Cell, 14, 3876–3887. https://doi.org/10.1091/mbc.e03-02-0090CrossRefPubMedPubMedCentral

17.

Sawyer, S. L., Cheng, I. H., Chai, W., & Tye, B. K. (2004). Mcm10 and Cdc45 cooperate in origin activation in Saccharomyces cerevisiae. Journal of Molecular Biology, 340, 195–202. https://doi.org/10.1016/j.jmb.2004.04.066CrossRefPubMed

18.

Heller, R. C., Kang, S., Lam, W. M., Chen, S., Chan, C. S., & Bell, S. P. (2011). Eukaryotic origin-dependent DNA replication in vitro reveals sequential action of DDK and S-CDK kinases. Cell, 146, 80–91. https://doi.org/10.1016/j.cell.2011.06.012CrossRefPubMedPubMedCentral

19.

Maine, G. T., Sinha, P., & Tye, B.-K. (1984). Mutants of s. cerevisiae defective in the maintenance of minichromosomes. Genetics, 106, 365–385. https://doi.org/10.1093/genetics/106.3.365CrossRefPubMedPubMedCentral

20.

Izumi, M., Yanagi, K., Mizuno, T., Yokoi, M., Kawasaki, Y., Moon, K.-Y., Hurwitz, J., Yatagai, F., & Hanaoka, F. (2000). The human homolog of Saccharomyces cerevisiae Mcm10 interacts with replication factors and dissociates from nuclease-resistant nuclear structures in G2 phase. Nucleic Acids Research, 28, 4769–4777.CrossRefPubMedPubMedCentral

21.

Homesley, L., Lei, M., Kawasaki, Y., Sawyer, S., Christensen, T., & Tye, B. K. (2000). Mcm10 and the MCM2–7 complex interact to initiate DNA synthesis and to release replication factors from origins. Genes & Development, 14, 913–926.CrossRef

22.

Fien, K., Cho, Y.-S., Lee, J.-K., Raychaudhuri, S., Tappin, I., & Hurwitz, J. (2004). Primer utilization by DNA polymerase alpha-primase is influenced by its interaction with Mcm10p. Journal of Biological Chemistry, 279, 16144–16153. https://doi.org/10.1074/jbc.M400142200CrossRefPubMed

23.

Das-Bradoo, S., Ricke, R. M., & Bielinsky, A.-K. (2006). Interaction between PCNA and Diubiquitinated Mcm10 Is Essential for Cell Growth in Budding Yeast. Molecular and Cellular Biology, 26, 4806–4817. https://doi.org/10.1128/MCB.02062-05CrossRefPubMedPubMedCentral

24.

Fernández-Cid, A., Riera, A., Tognetti, S., Herrera, M. C., Samel, S., Evrin, C., Winkler, C., Gardenal, E., Uhle, S., & Speck, C. (2013). An ORC/Cdc6/MCM2-7 complex is formed in a Multistep reaction to serve as a platform for MCM double-hexamer assembly. Molecular Cell, 50, 577–588. https://doi.org/10.1016/j.molcel.2013.03.026CrossRefPubMed

25.

Izumi, M., Yatagai, F., & Hanaoka, F. (2001). Cell cycle-dependent proteolysis and phosphorylation of human Mcm10. Journal of Biological Chemistry, 276, 48526–48531. https://doi.org/10.1074/jbc.M107190200CrossRefPubMed

26.

Simon, A. C., Zhou, J. C., Perera, R. L., van Deursen, F., Evrin, C., Ivanova, M. E., Kilkenny, M. L., Renault, L., Kjaer, S., Matak-Vinković, D., Labib, K., Costa, A., & Pellegrini, L. (2014). A Ctf4 trimer couples the CMG helicase to DNA polymerase α in the eukaryotic replisome. Nature, 510, 293–297. https://doi.org/10.1038/nature13234CrossRefPubMedPubMedCentral

27.

van Deursen, F., Sengupta, S., De Piccoli, G., Sanchez-Diaz, A., & Labib, K. (2012). Mcm10 associates with the loaded DNA helicase at replication origins and defines a novel step in its activation. EMBO Journal, 31, 2195–2206. https://doi.org/10.1038/emboj.2012.69CrossRefPubMedPubMedCentral

28.

Watase, G., Takisawa, H., & Kanemaki, M. T. (2012). Mcm10 plays a role in functioning of the eukaryotic replicative DNA helicase, Cdc45-Mcm-GINS. Curr. Biol. CB, 22, 343–349. https://doi.org/10.1016/j.cub.2012.01.023CrossRefPubMed

29.

Yeeles, J. T. P., Deegan, T. D., Janska, A., Early, A., & Diffley, J. F. X. (2015). Regulated eukaryotic DNA replication origin firing with purified proteins. Nature, 519, 431–435. https://doi.org/10.1038/nature14285CrossRefPubMedPubMedCentral

30.

Lõoke, M., Maloney, M. F., & Bell, S. P. (2017). Mcm10 regulates DNA replication elongation by stimulating the CMG replicative helicase. Genes & Development, 31, 291–305. https://doi.org/10.1101/gad.291336.116CrossRef

31.

Gambus, A., van Deursen, F., Polychronopoulos, D., Foltman, M., Jones, R. C., Edmondson, R. D., Calzada, A., & Labib, K. (2009). A key role for Ctf4 in coupling the MCM2-7 helicase to DNA polymerase α within the eukaryotic replisome. EMBO Journal, 28, 2992–3004. https://doi.org/10.1038/emboj.2009.226CrossRefPubMedPubMedCentral

32.

Im, J.-S., Ki, S.-H., Farina, A., Jung, D.-S., Hurwitz, J., & Lee, J.-K. (2009). 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 USA, 106, 15628–15632. https://doi.org/10.1073/pnas.0908039106CrossRef

33.

Karnani, N., & Dutta, A. (2011). The effect of the intra-S-phase checkpoint on origins of replication in human cells. Genes & Development, 25, 621–633. https://doi.org/10.1101/gad.2029711CrossRef

34.

Perez-Arnaiz, P., & Kaplan, D. L. (2016). An Mcm10 Mutant Defective in ssDNA Binding Shows Defects in DNA Replication Initiation. Journal of Molecular Biology, 428, 4608–4625. https://doi.org/10.1016/j.jmb.2016.10.014CrossRefPubMedPubMedCentral

35.

Douglas, M. E., & Diffley, J. F. X. (2016). Recruitment of Mcm10 to Sites of Replication Initiation Requires Direct Binding to the Minichromosome Maintenance (MCM) Complex *. Journal of Biological Chemistry, 291, 5879–5888. https://doi.org/10.1074/jbc.M115.707802CrossRefPubMed

36.

Baxley, R. M., & Bielinsky, A.-K. (2017). Mcm10: A Dynamic Scaffold at Eukaryotic Replication Forks. Genes, 8, 73. https://doi.org/10.3390/genes8020073CrossRefPubMedPubMedCentral

37.

Langston, L. D., Mayle, R., Schauer, G. D., Yurieva, O., Zhang, D., Yao, N. Y., Georgescu, R. E., & O’Donnell, M. E. (2017). Mcm10 promotes rapid isomerization of CMG-DNA for replisome bypass of lagging strand DNA blocks. eLife, 6, e29118. https://doi.org/10.7554/eLife.29118CrossRefPubMedPubMedCentral

38.

Deegan, T. D., Baxter, J., Ortiz Bazán, M. Á., Yeeles, J. T. P., & Labib, K. P. M. (2019). Pif1-family helicases support fork convergence during DNA replication termination in eukaryotes. Molecular Cell, 74, 231-244.e9. https://doi.org/10.1016/j.molcel.2019.01.040CrossRefPubMedPubMedCentral

39.

Hill, J., Eickhoff, P., Drury, L. S., Costa, A., & Diffley, J. F. X. (2020). The eukaryotic replisome requires an additional helicase to disarm dormant replication origins. bioRxiv, 17, 301366. https://doi.org/10.1101/2020.09.17.301366CrossRef

40.

Kawasaki, Y., Hiraga, S., & Sugino, A. (2000). Interactions between Mcm10p and other replication factors are required for proper initiation and elongation of chromosomal DNA replication in Saccharomyces cerevisiae. Genes to Cells, 5, 975–989. https://doi.org/10.1046/j.1365-2443.2000.00387.xCrossRefPubMed

41.

Liu, Q., Choe, W., & Campbell, J. L. (2000). Identification of the Xenopus laevis homolog of Saccharomyces cerevisiae DNA2 and its role in DNA replication. Journal of Biological Chemistry, 275, 1615–1624. https://doi.org/10.1074/jbc.275.3.1615CrossRefPubMed

42.

Zhu, W., Ukomadu, C., Jha, S., Senga, T., Dhar, S. K., Wohlschlegel, J. A., Nutt, L. K., Kornbluth, S., & Dutta, A. (2007). Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication. Genes & Development, 21, 2288–2299. https://doi.org/10.1101/gad.1585607CrossRef

43.

Ricke, R. M., & Bielinsky, A.-K. (2004). Mcm10 regulates the stability and chromatin association of DNA polymerase-alpha. Molecular Cell, 16, 173–185. https://doi.org/10.1016/j.molcel.2004.09.017CrossRefPubMed

44.

Chadha, G. S., Gambus, A., Gillespie, P. J., & Blow, J. J. (2016). Xenopus Mcm10 is a CDK-substrate required for replication fork stability. Cell Cycle Georget. Tex, 15, 2183–2195. https://doi.org/10.1080/15384101.2016.1199305CrossRef

45.

Henrikus, S. S., Gross, M. H., Willhoft, O., Pühringer, T., Lewis, J. S., McClure, A. W., Greiwe, J. F., Palm, G., Nans, A., Diffley, J. F. X., & Costa, A. (2024). Unwinding of a eukaryotic origin of replication visualized by cryo-EM. Nature Structural & Molecular Biology, 17, 1–12. https://doi.org/10.1038/s41594-024-01280-zCrossRef

46.

Wawrousek, K. E., Fortini, B. K., Polaczek, P., Chen, L., Liu, Q., Dunphy, W. G., & Campbell, J. L. (2010). Xenopus DNA2 is a helicase/nuclease that is found in complexes with replication proteins And-1/Ctf4 and Mcm10 and DSB response proteins Nbs1 and ATM. Cell Cycle Georget. Tex, 9, 1156–1166. https://doi.org/10.4161/cc.9.6.11049CrossRef

47.

Thu, Y. M., & Bielinsky, A.-K. (2013). Enigmatic roles of Mcm10 in DNA replication. Trends in Biochemical Sciences, 38, 184–194. https://doi.org/10.1016/j.tibs.2012.12.003CrossRefPubMedPubMedCentral

48.

Lee, C., Liachko, I., Bouten, R., Kelman, Z., & Tye, B. K. (2010). Alternative mechanisms for coordinating polymerase alpha and MCM helicase. Molecular and Cellular Biology, 30, 423–435. https://doi.org/10.1128/MCB.01240-09CrossRefPubMed

49.

Baxley, R. M., Leung, W., Schmit, M. M., Matson, J. P., Yin, L., Oram, M. K., Wang, L., Taylor, J., Hedberg, J., Rogers, C. B., Harvey, A. J., Basu, D., Taylor, J. C., Pagnamenta, A. T., Dreau, H., Craft, J., Ormondroyd, E., Watkins, H., Hendrickson, E. A., … Bielinsky, A.-K. (2021). Bi-allelic MCM10 variants associated with immune dysfunction and cardiomyopathy cause telomere shortening. Nature Communications, 12, 1626. https://doi.org/10.1038/s41467-021-21878-xCrossRefPubMedPubMedCentral

50.

Ibarra, A., Schwob, E., & Méndez, J. (2008). 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, 105, 8956–8961. https://doi.org/10.1073/pnas.0803978105CrossRefPubMedPubMedCentral

51.

Murayama, T., Takeuchi, Y., Yamawaki, K., Natsume, T., Li, M., Marcela, R.-C.N., Nishimura, T., Kogure, Y., Nakata, A., Tominaga, K., Sasahara, A., Yano, M., Ishikawa, S., Ohta, T., Ikeda, K., Horie-Inoue, K., Inoue, S., Seki, M., Suzuki, Y., … Gotoh, N. (2021). MCM10 compensates for Myc-induced DNA replication stress in breast cancer stem-like cells. Cancer Science, 112, 1209–1224. https://doi.org/10.1111/cas.14776CrossRefPubMedPubMedCentral

52.

Georgescu, R., Yuan, Z., Bai, L., de Luna Almeida, R., Santos, J., Sun, D., Zhang, O., Yurieva, H., & O’Donnell, M. E. (2017). Structure of eukaryotic CMG helicase at a replication fork and implications to replisome architecture and origin initiation. Proceedings of the National Academy of Sciences of the United States of America, 114, E697–E706. https://doi.org/10.1073/pnas.1620500114CrossRefPubMedPubMedCentral

53.

Vo, N., Anh Suong, D. N., Yoshino, N., Yoshida, H., Cotterill, S., & Yamaguchi, M. (2017). Novel roles of HP1a and Mcm10 in DNA replication, genome maintenance and photoreceptor cell differentiation. Nucleic Acids Research, 45, 1233–1254. https://doi.org/10.1093/nar/gkw1174CrossRefPubMed

54.

Liachko, I., & Tye, B. K. (2009). Mcm10 mediates the interaction between DNA replication and silencing machineries. Genetics, 181, 379–391. https://doi.org/10.1534/genetics.108.099101CrossRefPubMedPubMedCentral

55.

Deegan, T. D., Mukherjee, P. P., Fujisawa, R., Polo Rivera, C., & Labib, K. (2020). CMG helicase disassembly is controlled by replication fork DNA, replisome components and a ubiquitin threshold. eLife, 9, e60371. https://doi.org/10.7554/eLife.60371CrossRefPubMedPubMedCentral

56.

Tian, J., Lu, Z., Niu, S., Zhang, S., Ying, P., Wang, L., Zhang, M., Cai, Y., Dong, T., Zhu, Y., Zhong, R., Wang, Z., Chang, J., & Miao, X. (2021). Aberrant MCM10 SUMOylation induces genomic instability mediated by a genetic variant associated with survival of esophageal squamous cell carcinoma. Clinical and Translational Medicine, 11, e485. https://doi.org/10.1002/ctm2.485CrossRefPubMedPubMedCentral

57.

Lee, J.-K., Seo, Y.-S., & Hurwitz, J. (2003). The Cdc23 (Mcm10) protein is required for the phosphorylation of minichromosome maintenance complex by the Dfp1-Hsk1 kinase. Proceedings of the National Academy of Sciences USA, 100, 2334–2339. https://doi.org/10.1073/pnas.0237384100CrossRef

58.

Evrin, C., Clarke, P., Zech, J., Lurz, R., Sun, J., Uhle, S., Li, H., Stillman, B., & Speck, C. (2009). A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication. Proceedings of the National Academy of Sciences USA, 106, 20240–20245. https://doi.org/10.1073/pnas.0911500106CrossRef

59.

Nguyen, V. Q., Co, C., & Li, J. J. (2001). Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms. Nature, 411, 1068–1073. https://doi.org/10.1038/35082600CrossRefPubMed

60.

Langston, L. D., & O’Donnell, M. E. (2019). An explanation for origin unwinding in eukaryotes. eLife, 8, e46515. https://doi.org/10.7554/eLife.46515CrossRefPubMedPubMedCentral

61.

Wasserman, M. R., Schauer, G. D., O’Donnell, M. E., & Liu, S. (2019). Replication Fork Activation Is Enabled by a Single-Stranded DNA Gate in CMG Helicase. Cell, 178, 600-611.e16. https://doi.org/10.1016/j.cell.2019.06.032CrossRefPubMedPubMedCentral

62.

Xu, X., Rochette, P. J., Feyissa, E. A., Su, T. V., & Liu, Y. (2009). MCM10 mediates RECQ4 association with MCM2-7 helicase complex during DNA replication. EMBO Journal, 28, 3005–3014. https://doi.org/10.1038/emboj.2009.235CrossRefPubMedPubMedCentral

63.

Kliszczak, M., Sedlackova, H., Pitchai, G. P., Streicher, W. W., Krejci, L., & Hickson, I. D. (2015). Interaction of RECQ4 and MCM10 is important for efficient DNA replication origin firing in human cells. Oncotarget, 6, 40464–40479. https://doi.org/10.18632/oncotarget.6342CrossRefPubMedPubMedCentral

64.

Xiang, S., Luo, X., Welch, D., Reed, D. R., & Alexandrow, M. G. (2023). Identification of selective ATP-competitive CMG helicase inhibitors for cancer intervention that disrupt CMG-replisome function. Research Square, 11, 355–3182731. https://doi.org/10.21203/rs.3.rs-3182731/v1CrossRef

65.

Bruck, I., & Kaplan, D. (2009). Dbf4-Cdc7 Phosphorylation of Mcm2 Is Required for Cell Growth. Journal of Biological Chemistry, 284, 28823–28831. https://doi.org/10.1074/jbc.M109.039123CrossRefPubMedPubMedCentral

66.

Brosh, R. M., & Trakselis, M. A. (2019). Fine-tuning of the replisome: Mcm10 regulates fork progression and regression. Cell Cycle, 18, 1047–1055. https://doi.org/10.1080/15384101.2019.1609833CrossRefPubMedPubMedCentral

67.

Ricke, R. M., & Bielinsky, A.-K. (2006). A Conserved Hsp10-like Domain in Mcm10 Is Required to Stabilize the Catalytic Subunit of DNA Polymerase-α in Budding Yeast *. Journal of Biological Chemistry, 281, 18414–18425. https://doi.org/10.1074/jbc.M513551200CrossRefPubMed

68.

Perez-Arnaiz, P., Bruck, I., Colbert, M. K., & Kaplan, D. L. (2017). An intact Mcm10 coiled-coil interaction surface is important for origin melting, helicase assembly and the recruitment of Pol-α to Mcm2-7. Nucleic Acids Research, 45, 7261–7275. https://doi.org/10.1093/nar/gkx438CrossRefPubMedPubMedCentral

69.

Im, J.-S., Park, S.-Y., Cho, W.-H., Bae, S.-H., Hurwitz, J., & Lee, J.-K. (2015). RecQL4 is required for the association of Mcm10 and Ctf4 with replication origins in human cells. Cell Cycle, 14, 1001–1009. https://doi.org/10.1080/15384101.2015.1007001CrossRefPubMedPubMedCentral

70.

Aves, S. J., Tongue, N., Foster, A. J., & Hart, E. A. (1998). The essential schizosaccharomyces pombe cdc23 DNA replication gene shares structural and functional homology with the Saccharomyces cerevisiae DNA43 (MCM10) gene. Current Genetics, 34, 164–171. https://doi.org/10.1007/s002940050382CrossRefPubMed

71.

Locovei, A. M., Spiga, M.-G., Tanaka, K., Murakami, Y., & D’Urso, G. (2006). The CENP-B homolog, Abp1, interacts with the initiation protein Cdc23 (MCM10) and is required for efficient DNA replication in fission yeast. Cell Division, 1, 27. https://doi.org/10.1186/1747-1028-1-27CrossRefPubMedPubMedCentral

72.

Taylor, M., Moore, K., Murray, J., Aves, S. J., & Price, C. (2011). Mcm10 interacts with Rad4/Cut5(TopBP1) and its association with origins of DNA replication is dependent on Rad4/Cut5(TopBP1). DNA Repair, 10, 1154–1163. https://doi.org/10.1016/j.dnarep.2011.09.001CrossRefPubMed

73.

Robertson, P. D., Warren, E. M., Zhang, H., Friedman, D. B., Lary, J. W., Cole, J. L., Tutter, A. V., Walter, J. C., Fanning, E., & Eichman, B. F. (2008). Domain architecture and biochemical characterization of vertebrate Mcm10. Journal of Biological Chemistry, 283, 3338–3348. https://doi.org/10.1074/jbc.M706267200CrossRefPubMed

74.

Douglas, M. E., Ali, F. A., Costa, A., & Diffley, J. F. X. (2018). The mechanism of eukaryotic CMG helicase activation. Nature, 555, 265–268. https://doi.org/10.1038/nature25787CrossRefPubMedPubMedCentral

75.

Izumi, M., Mizuno, T., Yanagi, K.-I., Sugimura, K., Okumura, K., Imamoto, N., Abe, T., & Hanaoka, F. (2017). The Mcm2-7-interacting domain of human mini-chromosome maintenance 10 (Mcm10) protein is important for stable chromatin association and origin firing. Journal of Biological Chemistry, 292, 13008–13021. https://doi.org/10.1074/jbc.M117.779371CrossRefPubMedPubMedCentral

76.

Campos, L. V., Van Ravenstein, S. X., Vontalge, E. J., Greer, B. H., Heintzman, D. R., Kavlashvili, T., McDonald, W. H., Rose, K. L., Eichman, B. F., & Dewar, J. M. (2023). RTEL1 and MCM10 overcome topological stress during vertebrate replication termination. Cell Reports, 42, 112109. https://doi.org/10.1016/j.celrep.2023.112109CrossRefPubMed

77.

Rhind, N. (2006). DNA replication timing: Random thoughts about origin firing. Nature Cell Biology, 8, 1313–1316. https://doi.org/10.1038/ncb1206-1313CrossRefPubMedPubMedCentral

78.

Wang, W., Klein, K. N., Proesmans, K., Yang, H., Marchal, C., Zhu, X., Borrman, T., Hastie, A., Weng, Z., Bechhoefer, J., Chen, C.-L., Gilbert, D. M., & Rhind, N. (2021). Genome-wide mapping of human DNA replication by optical replication mapping supports a stochastic model of eukaryotic replication. Molecular Cell, 81, 2975-2988.e6. https://doi.org/10.1016/j.molcel.2021.05.024CrossRefPubMedPubMedCentral

79.

Windhager, J., Paine, A., Nathanailidou, P., Tasiudi, E., Martínez, M. R., Lygeros, J., Lygerou, Z., & Rapsomaniki, M. A. (2019). A stochastic hybrid model of DNA replication incorporating 3D protein mobility dynamics. BioRxiv, 583187. https://doi.org/10.1101/583187

80.

Das, S. P., Borrman, T., Liu, V. W. T., Yang, S.C.-H., Bechhoefer, J., & Rhind, N. (2015). Replication timing is regulated by the number of MCMs loaded at origins. Genome Research, 25, 1886–1892. https://doi.org/10.1101/gr.195305.115CrossRefPubMedPubMedCentral

81.

Caballero, M., Ge, T., Rebelo, A. R., Seo, S., Kim, S., Brooks, K., Zuccaro, M., Kanagaraj, R., Vershkov, D., Kim, D., Smogorzewska, A., Smolka, M., Benvenisty, N., West, S. C., Egli, D., Mace, E. M., & Koren, A. (2022). Comprehensive analysis of DNA replication timing across 184 cell lines suggests a role for MCM10 in replication timing regulation. Human Molecular Genetics, 31, 2899–2917. https://doi.org/10.1093/hmg/ddac082CrossRefPubMedPubMedCentral

82.

Peycheva, M., Neumann, T., Malzl, D., Nazarova, M., Schoeberl, U. E., & Pavri, R. (2022). DNA replication timing directly regulates the frequency of oncogenic chromosomal translocations. Science, 377, eabj5502. https://doi.org/10.1126/science.abj5502CrossRefPubMed

83.

Orr, S., Gaymes, T., Ladon, D., Chronis, C., Czepulkowski, B., Wang, R., Mufti, G., Marcotte, E., & Thomas, N. (2010). Reducing MCM levels in human primary T cells during the G0→G1 transition causes genomic instability during the first cell cycle. Oncogene, 29, 3803–3814. https://doi.org/10.1038/onc.2010.138CrossRefPubMedPubMedCentral

84.

Xu, X., Hua, X., Brown, K., Ren, X., & Zhang, Z. (2022). Mcm2 promotes stem cell differentiation via its ability to bind H3–H4. ELife, 11, e80917. https://doi.org/10.7554/eLife.80917CrossRefPubMedPubMedCentral

85.

Cacialli, P., Dogan, S., Linnerz, T., Pasche, C., & Bertrand, J. Y. (2023). Minichromosome maintenance protein 10 (mcm10) regulates hematopoietic stem cell emergence in the zebrafish embryo. Stem Cell Rep., 18, 1534–1546. https://doi.org/10.1016/j.stemcr.2023.05.022CrossRef

86.

Zhao, X., Wang, J., Jin, D., Cheng, J., Chen, H., Li, Z., Wang, Y., Lou, H., Zhu, J.-K., Du, X., & Gong, Z. (2023). AtMCM10 promotes DNA replication-coupled nucleosome assembly in Arabidopsis. Journal of Integrative Plant Biology, 65, 203–222. https://doi.org/10.1111/jipb.13438CrossRefPubMed

87.

Christensen, T. W., & Tye, B. K. (2003). Drosophila Mcm10 interacts with members of the prereplication complex and is required for proper chromosome condensation. Molecular Biology of the Cell, 14, 2206–2215. https://doi.org/10.1091/mbc.e02-11-0706CrossRefPubMedPubMedCentral

88.

Fatoba, S. T., Tognetti, S., Berto, M., Leo, E., Mulvey, C. M., Godovac-Zimmermann, J., Pommier, Y., & Okorokov, A. L. (2013). Human SIRT1 regulates DNA binding and stability of the Mcm10 DNA replication factor via deacetylation. Nucleic Acids Research, 41, 4065–4079. https://doi.org/10.1093/nar/gkt131CrossRefPubMedPubMedCentral

89.

Alver, R. C., Zhang, T., Josephrajan, A., Fultz, B. L., Hendrix, C. J., Das-Bradoo, S., & Bielinsky, A.-K. (2014). The N-terminus of Mcm10 is important for interaction with the 9–1-1 clamp and in resistance to DNA damage. Nucleic Acids Research, 42, 8389–8404. https://doi.org/10.1093/nar/gku479CrossRefPubMedPubMedCentral

90.

Quan, Y., Xia, Y., Liu, L., Cui, J., Li, Z., Cao, Q., Chen, X. S., Campbell, J. L., & Lou, H. (2015). Cell-cycle-regulated interaction between Mcm10 and double hexameric Mcm2-7 is required for helicase splitting and activation during S phase. Cell Reports, 13, 2576–2586. https://doi.org/10.1016/j.celrep.2015.11.018CrossRefPubMed

91.

Di Perna, R., Aria, V., De Falco, M., Sannino, V., Okorokov, A. L., Pisani, F. M., & De Felice, M. (2013). The physical interaction of Mcm10 with Cdc45 modulates their DNA-binding properties. The Biochemical Journal, 454, 333–343. https://doi.org/10.1042/BJ20130059CrossRefPubMed

92.

Cook, C. R., Kung, G., Peterson, F. C., Volkman, B. F., & Lei, M. (2003). A Novel Zinc Finger Is Required for Mcm10 Homocomplex Assembly *. Journal of Biological Chemistry, 278, 36051–36058. https://doi.org/10.1074/jbc.M306049200CrossRefPubMed

93.

Du, W., Stauffer, M. E., & Eichman, B. F. (2012). Structural Biology of Replication Initiation Factor Mcm10 (pp. 197–216). In S. MacNeill (Ed.), Eukaryot. Replisome Guide Protein Struct. Funct., Springer Netherlands, Dordrecht. https://doi.org/10.1007/978-94-007-4572-8_11

94.

Burich, R., & Lei, M. (2003). Two bipartite NLSs mediate constitutive nuclear localization of Mcm10. Current Genetics, 44, 195–201. https://doi.org/10.1007/s00294-003-0443-yCrossRefPubMed

95.

Apger, J., Reubens, M., Henderson, L., Gouge, C. A., Ilic, N., Zhou, H. H., & Christensen, T. W. (2010). Multiple functions for drosophila Mcm10 suggested through analysis of two Mcm10 mutant alleles. Genetics, 185, 1151–1165. https://doi.org/10.1534/genetics.110.117234CrossRefPubMedPubMedCentral

96.

Liachko, I., & Tye, B. K. (2005). Mcm10 is required for the maintenance of transcriptional silencing in Saccharomyces cerevisiae. Genetics, 171, 503–515. https://doi.org/10.1534/genetics.105.042333CrossRefPubMedPubMedCentral

97.

Douglas, N. L., Dozier, S. K., & Donato, J. J. (2005). Dual Roles for Mcm10 in DNA Replication Initiation and Silencing at the Mating-type Loci. Molecular Biology Reports, 32, 197–204. https://doi.org/10.1007/s11033-005-2312-xCrossRefPubMed

98.

Albertson, D. G. (2006). Gene amplification in cancer. Trends in Genetics, 22, 447–455. https://doi.org/10.1016/j.tig.2006.06.007CrossRefPubMed

99.

Thu, Y. M., & Bielinsky, A.-K. (2014). MCM10: one tool for all - integrity, maintenance and damage control. Seminars in Cell and Developmental Biology, 30, 121–130. https://doi.org/10.1016/j.semcdb.2014.03.017CrossRefPubMed

100.

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

101.

Shao, M., Yang, S., & Dong, S. (2021). High expression of MCM10 is predictive of poor outcomes in lung adenocarcinoma. PeerJ, 9, e10560. https://doi.org/10.7717/peerj.10560CrossRefPubMedPubMedCentral

102.

Wu, Z., Wang, Y., Li, J., Wang, H., Tuo, X., & Zheng, J. (2022). MCM10 is a prognostic biomarker and correlated with immune checkpoints in ovarian cancer. Frontiers in Genetics, 13, 864578. https://www.frontiersin.org/articles/10.3389/fgene.2022.864578 (Accessed September 2, 2022).

103.

Xiang, S., Reed, D. R., & Alexandrow, M. G. (2023). The CMG helicase and cancer: A tumor “engine” and weakness with missing mutations. Oncogene, 42, 473–490. https://doi.org/10.1038/s41388-022-02572-8CrossRefPubMed

104.

Baxley, R. M., Thu, Y. M., & Bielinsky, A. K. (2016). The role of Mcm10 in replication initiation (pp. 319–341). In D.L. Kaplan (Ed.), Initiat. DNA Replication Eukaryotes, Springer International Publishing, Cham. https://doi.org/10.1007/978-3-319-24696-3_16

105.

Shen, Z. (2011). Genomic instability and cancer: An introduction. Journal of Molecular Cell Biology, 3, 1–3. https://doi.org/10.1093/jmcb/mjq057CrossRefPubMed

106.

Mace, E. M., Paust, S., Conte, M. I., Baxley, R. M., Schmit, M. M., Patil, S. L., Guilz, N. C., Mukherjee, M., Pezzi, A. E., Chmielowiec, J., Tatineni, S., Chinn, I. K., Akdemir, Z. C., Jhangiani, S. N., Muzny, D. M., Stray-Pedersen, A., Bradley, R. E., Moody, M., Connor, P. P., … Orange, J. S. (2020). Human NK cell deficiency as a result of biallelic mutations in MCM10. The Journal of Clinical Investigation, 130, 5272–5286. https://doi.org/10.1172/JCI134966CrossRefPubMedPubMedCentral

107.

Zeman, M. K., & Cimprich, K. A. (2014). Causes and consequences of replication stress. Nature Cell Biology, 16, 2–9. https://doi.org/10.1038/ncb2897CrossRefPubMedPubMedCentral

108.

Drissi, R., Chauvin, A., McKenna, A., Lévesque, D., Blais-Brochu, S., Jean, D., & Boisvert, F.-M. (2018). Destabilization of the MiniChromosome Maintenance (MCM) complex modulates the cellular response to DNA double strand breaks. Cell Cycle Georget Tex, 17, 2593–2609. https://doi.org/10.1080/15384101.2018.1553336CrossRef

109.

Kaur, M., Khan, M. D. M., Kar, A., Sharma, A., & Saxena, S. (2012). CRL4–DDB1–VPRBP ubiquitin ligase mediates the stress triggered proteolysis of Mcm10. Nucleic Acids Research, 40, 7332–7346. https://doi.org/10.1093/nar/gks366CrossRefPubMedPubMedCentral

110.

Jevitt, A. M., Rankin, B. D., Chen, J., & Rankin, S. (2023). The cohesin modifier ESCO2 is stable during DNA replication. Chromosome Research, 31, 6. https://doi.org/10.1007/s10577-023-09711-1CrossRefPubMedPubMedCentral

111.

Lopes, M., Foiani, M., & Sogo, J. M. (2006). Multiple Mechanisms Control Chromosome Integrity after Replication Fork Uncoupling and Restart at Irreparable UV Lesions. Molecular Cell, 21, 15–27. https://doi.org/10.1016/j.molcel.2005.11.015CrossRefPubMed

112.

McClure, A. W., & Diffley, J. F. (2021). Rad53 checkpoint kinase regulation of DNA replication fork rate via Mrc1 phosphorylation. eLife, 10, e69726. https://doi.org/10.7554/eLife.69726

113.

Kaur, M., Sharma, A., Khan, M., Kar, A., & Saxena, S. (2010). Mcm10 proteolysis initiates before the onset of M-phase. BMC Cell Biology, 11, 84. https://doi.org/10.1186/1471-2121-11-84CrossRefPubMedPubMedCentral

114.

Guilz, N. C. Ahn, Y. O., Fatima, H., Pedroza, L. A., Seo, S., Soni, R. K., Wang, N., Egli, D., & Mace, E. M. (2024). Replication stress in activated human NK cells induces sensitivity to apoptosis. Replication Stress in Activated Human NK Cells Induces Sensitivity to Apoptosis. Journal of Immunology (Baltimore, Md. : 1950), 213(1), 40–51. https://doi.org/10.4049/jimmunol.2300843

115.

Schmit, M., & Bielinsky, A.-K. (2021). Congenital Diseases of DNA Replication: Clinical Phenotypes and Molecular Mechanisms. International Journal of Molecular Sciences, 22, E911. https://doi.org/10.3390/ijms22020911CrossRef

116.

Schmit, M. M., Baxley, R. M., Wang, L., Hinderlie, P., Kaufman, M., Simon, E., Raju, A., Miller, J. S., & Bielinsky, A.-K. (2024). A critical threshold of MCM10 is required to maintain genome stability during differentiation of induced pluripotent stem cells into natural killer cells. Open Biology, 14, 230407. https://doi.org/10.1098/rsob.230407CrossRefPubMedPubMedCentral

117.

Kalimutho, M., Nones, K., Srihari, S., Duijf, P. H. G., Waddell, N., & Khanna, K. K. (2019). Patterns of Genomic Instability in Breast Cancer. Trends in Pharmacological Sciences, 40, 198–211. https://doi.org/10.1016/j.tips.2019.01.005CrossRefPubMed

118.

Kang, Z., Fu, P., Alcivar, A. L., Fu, H., Redon, C., Foo, T. K., Zuo, Y., Ye, C., Baxley, R., Madireddy, A., Buisson, R., Bielinsky, A.-K., Zou, L., Shen, Z., Aladjem, M. I., & Xia, B. (2021). BRCA2 associates with MCM10 to suppress PRIMPOL-mediated repriming and single-stranded gap formation after DNA damage. Nature Communications, 12, 5966. https://doi.org/10.1038/s41467-021-26227-6CrossRefPubMedPubMedCentral

119.

Das, M., Prasad, S. B., Yadav, S. S., Govardhan, H. B., Pandey, L. K., Singh, S., Pradhan, S., & Narayan, G. (2013). Over Expression of Minichromosome Maintenance Genes is Clinically Correlated to Cervical Carcinogenesis. PLoS ONE, 8, e69607. https://doi.org/10.1371/journal.pone.0069607CrossRefPubMedPubMedCentral

120.

Chattopadhyay, S., & Bielinsky, A.-K. (2007). Human Mcm10 Regulates the Catalytic Subunit of DNA Polymerase-α and Prevents DNA Damage during Replication. Molecular Biology of the Cell, 18, 4085–4095. https://doi.org/10.1091/mbc.E06-12-1148CrossRefPubMedPubMedCentral

121.

Park, J. H., Bang, S. W., Kim, S. H., & Hwang, D. S. (2008). Knockdown of human MCM10 activates G2 checkpoint pathway. Biochemical and Biophysical Research Communications, 365, 490–495. https://doi.org/10.1016/j.bbrc.2007.11.004CrossRefPubMed

122.

Lim, H. J., Jeon, Y., Jeon, C. H., Kim, J. H., & Lee, H. (1813). Targeted disruption of Mcm10 causes defective embryonic cell proliferation and early embryo lethality. Biochimica et Biophysica Acta, 2011, 1777–1783. https://doi.org/10.1016/j.bbamcr.2011.05.012CrossRef

123.

Pilié, P. G., Tang, C., Mills, G. B., & Yap, T. A. (2019). State-of-the-art strategies for targeting the DNA damage response in cancer. Nature Reviews. Clinical Oncology, 16, 81–104. https://doi.org/10.1038/s41571-018-0114-zCrossRefPubMedPubMedCentral

124.

Zou, L., & Elledge, S. J. (2003). Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes. Science, 300, 1542–1548. https://doi.org/10.1126/science.1083430CrossRefPubMed

125.

Cobb, J. A., Schleker, T., Rojas, V., Bjergbaek, L., Tercero, J. A., & Gasser, S. M. (2005). Replisome instability, fork collapse, and gross chromosomal rearrangements arise synergistically from Mec1 kinase and RecQ helicase mutations. Genes & Development, 19, 3055–3069. https://doi.org/10.1101/gad.361805CrossRef

126.

Mayle, R., Langston, L., Molloy, K. R., Zhang, D., Chait, B. T., & O’Donnell, M. E. (2019). Mcm10 has potent strand-annealing activity and limits translocase-mediated fork regression. Proceedings of the National Academy of Sciences of the United States of America, 116, 798–803. https://doi.org/10.1073/pnas.1819107116CrossRefPubMed

127.

Tanaka, S., & Ogawa, S. (2022). Dimerization of Firing Factors for Replication Origin Activation in Eukaryotes: A Crucial Process for Simultaneous Assembly of Bidirectional Replication Forks? Biology, 11, 928. https://doi.org/10.3390/biology11060928CrossRefPubMedPubMedCentral

128.

Cui, F., Hu, J., Ning, S., Tan, J., & Tang, H. (2018). Overexpression of MCM10 promotes cell proliferation and predicts poor prognosis in prostate cancer. The Prostate, 78, 1299–1310. https://doi.org/10.1002/pros.23703CrossRefPubMedPubMedCentral

129.

Chee, C. W., Mohd Hashim, N., Abdullah, I., & Nor Rashid, N. (2024). RNA sequencing and bioinformatics analysis reveals the downregulation of DNA replication genes by morindone in colorectal cancer cells. Biotechnology and Applied Biochemistry, 196, 3216–3233. https://doi.org/10.1007/s12010-023-04690-9CrossRef

130.

Sun, M., Guo, X., Qian, X., Wang, H., Yang, C., Brinkman, K. L., Serrano-Gonzalez, M., Jope, R. S., Zhou, B., Engler, D. A., Zhan, M., Wong, S. T. C., Fu, L., & Xu, B. (2012). Activation of the ATM-Snail pathway promotes breast cancer metastasis. Journal of Molecular Cell Biology, 4, 304–315. https://doi.org/10.1093/jmcb/mjs048CrossRefPubMedPubMedCentral

131.

Grille, S. J., Bellacosa, A., Upson, J., Klein-Szanto, A. J., van Roy, F., Lee-Kwon, W., Donowitz, M., Tsichlis, P. N., & Larue, L. (2003). The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Research, 63, 2172–2178.PubMed

132.

Koppen, A., Ait-Aissa, R., Koster, J., van Sluis, P. G., Ora, I., Caron, H. N., Volckmann, R., Versteeg, R., & Valentijn, L. J. (2007). Direct regulation of the minichromosome maintenance complex by MYCN in neuroblastoma. European Journal of Cancer, 1990(43), 2413–2422. https://doi.org/10.1016/j.ejca.2007.07.024CrossRef

133.

Schuldiner, O., & Benvenisty, N. (2001). A DNA microarray screen for genes involved in c-MYC and N-MYC oncogenesis in human tumors. Oncogene, 20, 4984–4994. https://doi.org/10.1038/sj.onc.1204459CrossRefPubMed

134.

Yoshida, K., & Inoue, I. (2004). Expression of MCM10 and TopBP1 is regulated by cell proliferation and UV irradiation via the E2F transcription factor. Oncogene, 23, 6250–6260. https://doi.org/10.1038/sj.onc.1207829CrossRefPubMed

135.

Shtutman, M., Zhurinsky, J., Simcha, I., Albanese, C., D’Amico, M., Pestell, R., & Ben-Ze’ev, A. (1999). The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proceedings of the National Academy of Sciences of the United States of America, 96, 5522–5527. https://doi.org/10.1073/pnas.96.10.5522CrossRefPubMedPubMedCentral

136.

Wang, M., Xie, S., Yuan, W., Xie, T., Jamal, M., Huang, J., Yin, Q., Song, H., & Zhang, Q. (2019). Minichromosome maintenance protein 10 as a marker for proliferation and prognosis in lung cancer. International Journal of Oncology, 55, 1349–1360. https://doi.org/10.3892/ijo.2019.4899CrossRefPubMed

137.

Mahadevappa, R., Neves, H., Yuen, S. M., Jameel, M., Bai, Y., Yuen, H.-F., Zhang, S.-D., Zhu, Y., Lin, Y., & Kwok, H. F. (2018). DNA Replication Licensing Protein MCM10 Promotes Tumor Progression and Is a Novel Prognostic Biomarker and Potential Therapeutic Target in Breast Cancer. Cancers, 10, 282. https://doi.org/10.3390/cancers10090282CrossRefPubMedPubMedCentral

138.

Peng, Y.-P., Zhu, Y., Yin, L.-D., Zhang, J.-J., Guo, S., Fu, Y., Miao, Y., & Wei, J.-S. (2016). The Expression and Prognostic Roles of MCMs in Pancreatic Cancer. PLoS ONE, 11, e0164150. https://doi.org/10.1371/journal.pone.0164150CrossRefPubMedPubMedCentral

139.

Ahmed, S. M. Q., Laha, S., Das, R., Ifthikar, M. A., & Das, S. P. (2023). MCM10 expression is linked to cervical cancer aggressiveness. Frontiers in Molecular Medicine, 3, 1009903. https://www.frontiersin.org/articles/10.3389/fmmed.2023.1009903 (Accessed March 7, 2023).

140.

García-Aragoncillo, E., Carrillo, J., Lalli, E., Agra, N., Gómez-López, G., Pestaña, A., & Alonso, J. (2008). DAX1, a direct target of EWS/FLI1 oncoprotein, is a principal regulator of cell-cycle progression in Ewing’s tumor cells. Oncogene, 27, 6034–6043. https://doi.org/10.1038/onc.2008.203CrossRefPubMed

141.

Li, W. M., Huang, C. N., Ke, H. L., Li, C. C., Wei, Y. C., Yeh, H. C., Chang, L. L., Huang, C. H., Liang, P. I., Yeh, B. W., Chan, T. C., Li, C. F., & Wu, W. J. (2016). MCM10 overexpression implicates adverse prognosis in urothelial carcinoma. Oncotarget, 7, 77777–77792. https://doi.org/10.18632/oncotarget.12795.

142.

Hua, H., Kong, Q., Yin, J., Zhang, J., & Jiang, Y. (2020). Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: A challenge for cancer therapy. Journal of Hematology and Oncology, 13, 64. https://doi.org/10.1186/s13045-020-00904-3CrossRefPubMedPubMedCentral

143.

Kang, P., Han, Z., Liao, Z., Zhang, H., Jia, W., & Tian, Y. (2020). Knockdown of MCM10 gene impairs glioblastoma cell proliferation, migration and invasion and the implications for the regulation of tumorigenesis. Journal of Molecular Neuroscience, 70, 759–768. https://doi.org/10.1007/s12031-020-01486-yCrossRefPubMed

144.

Wotschofsky, Z., Gummlich, L., Liep, J., Stephan, C., Kilic, E., Jung, K., Billaud, J.-N., & Meyer, H.-A. (2016). Integrated microRNA and mRNA signature associated with the transition from the locally confined to the metastasized clear cell renal cell carcinoma exemplified by miR-146-5p. PLoS ONE, 11, e0148746. https://doi.org/10.1371/journal.pone.0148746CrossRefPubMedPubMedCentral

145.

Chen, Y.-R., Li, Y.-T., Wang, M.-Q., & Zhu, S.-L. (2021). Prognostic significance and function of MCM10 in human hepatocellular carcinoma. Future Oncology, 17, 4457–4470. https://doi.org/10.2217/fon-2021-0225CrossRefPubMed

146.

Zhang, W., Huang, F., Tang, X., & Ran, L. (2022). The clonal expression genes associated with poor prognosis of liver cancer. Frontiers in Genetics, 13, 808273. https://doi.org/10.3389/fgene.2022.808273CrossRefPubMedPubMedCentral

147.

Wan, W., Shen, Y., & Li, Q. (2020). MCM10 acts as a potential prognostic biomarker and promotes cell proliferation in hepatocellular carcinoma: Integrated bioinformatics analysis and experimental validation. Cancer Management and Research, 12, 9609–9619. https://doi.org/10.2147/CMAR.S267493CrossRefPubMedPubMedCentral

148.

Li, S., Jiang, Z., Li, Y., & Xu, Y. (2019). Prognostic significance of minichromosome maintenance mRNA expression in human lung adenocarcinoma. Oncology Reports, 42, 2279–2292. https://doi.org/10.3892/or.2019.7330CrossRefPubMedPubMedCentral

149.

Zhou, J., Wang, M., Zhou, Z., Wang, W., Duan, J., & Wu, G. (2021). Expression and Prognostic Value of MCM Family Genes in Osteosarcoma. Frontiers in Molecular Biosciences, 8, 668402. https://doi.org/10.3389/fmolb.2021.668402CrossRefPubMedPubMedCentral

150.

Hua, C., Zhao, G., Li, Y., & Bie, L. (2014). Minichromosome Maintenance (MCM) Family as potential diagnostic and prognostic tumor markers for human gliomas. BMC Cancer, 14, 526. https://doi.org/10.1186/1471-2407-14-526CrossRefPubMedPubMedCentral

151.

Zhou, J., Liu, F., Tian, L., Yang, M., Tan, J., Liu, X., Li, P., Chen, J., Chen, G., Xu, L., Peng, L., Wu, Q., & Zou, Y. (2023). Mutational analysis of minichromosome maintenance complex component (MCM) family genes in Chinese Han women with polycystic ovarian syndrome. Gynecological Endocrinology Official Journal of International Society of Gynecological Endocrinology, 39, 2206912. https://doi.org/10.1080/09513590.2023.2206912CrossRef

152.

Chen, J., Wu, S., Wang, J., Han, C., Zhao, L., He, K., Jia, Y., & Cui, M. (2023). MCM10: An effective treatment target and a prognostic biomarker in patients with uterine corpus endometrial carcinoma. Journal of Cellular and Molecular Medicine, 27, 1708–1724. https://doi.org/10.1111/jcmm.17772CrossRefPubMedPubMedCentral

153.

Tian, Q.-S., Zhang, Q., & Huang, W. (2023). MCM10 as a novel prognostic biomarker and its relevance to immune infiltration in gliomas. Technology and Health Care: Official Journal of European Society For Emergency Medicine, 31, 1301–1317. https://doi.org/10.3233/THC-220576CrossRef

154.

Guney, G., Taşkın, M. I., Sener, N., Tolu, E., Dodurga, Y., Elmas, L., Cetin, O., & Sarigul, C. (2022). The role of ERK-1 and ERK-2 gene polymorphisms in PCOS pathogenesis. Reproductive Biology and Endocrinology, 20, 95. https://doi.org/10.1186/s12958-022-00967-6CrossRefPubMedPubMedCentral

155.

Paulson, C. N., John, K., Baxley, R. M., Kurniawan, F., Orellana, K., Francis, R., Sobeck, A., Eichman, B. F., Chazin, W. J., Aihara, H., Georg, G. I., Hawkinson, J. E., & Bielinsky, A.-K. (2019). The anti-parasitic agent suramin and several of its analogues are inhibitors of the DNA binding protein Mcm10. Open Biology, 9, 190117. https://doi.org/10.1098/rsob.190117CrossRefPubMedPubMedCentral

156.

Araki, Y., Kawasaki, Y., Sasanuma, H., Tye, B. K., & Sugino, A. (2003). Budding yeast mcm10/dna43 mutant requires a novel repair pathway for viability. Genes to Cells, 8, 465–480. https://doi.org/10.1046/j.1365-2443.2003.00648.xCrossRefPubMed

157.

Ge, X. Q., Jackson, D. A., & Blow, J. J. (2007). Dormant origins licensed by excess Mcm2–7 are required for human cells to survive replicative stress. Genes & Development, 21, 3331–3341. https://doi.org/10.1101/gad.457807CrossRef

158.

Valenzuela, M. S., Hu, L., Lueders, J., Walker, R., & Meltzer, P. S. (2012). Broader utilization of origins of DNA replication in cancer cell lines along a 78 kb region of human chromosome 2q34. Journal of Cellular Biochemistry, 113, 132–140. https://doi.org/10.1002/jcb.23336CrossRefPubMedPubMedCentral

159.

Böhly, N., Schmidt, A.-K., Zhang, X., Slusarenko, B. O., Hennecke, M., Kschischo, M., & Bastians, H. (2022). Increased replication origin firing links replication stress to whole chromosomal instability in human cancer. Cell Reports, 41, 111836. https://doi.org/10.1016/j.celrep.2022.111836CrossRefPubMed

160.

Abdel-Maksoud, M. A., Iqbal, K., Gull, S., Kumar, S. K., Mastoor, M., Almutairi, S. M., Almanaa, T. N., Alfuraydi, A. A., Mubarak, A., Kotob, M. H., Jamil, M., & Zaky, M. Y. (2023). Immune modulation and prognostic significance of MCM10 in pan-cancer: A comprehensive analysis. Am. J. Transl. Res., 15, 6451–6463.PubMedPubMedCentral

161.

Alghamdi, Y. S., Mashraqi, M. M., Alsalmi, O., Alharthi, A. A., & Gharib, A. F. (2024). Multitargeted Docking, DFT-Based Optimisation, Pharmacokinetics, and MD Simulation Reveal 6-Oxidopamine HBr as a Multitargeted Inhibitor of Cervical Cancer Proteins. Current Medicinal Chemistry. https://doi.org/10.2174/0109298673289824240529063416CrossRefPubMed

Title: Multifaceted role of the DNA replication protein MCM10 in maintaining genome stability and its implication in human diseases
Authors: Sumayyah M. Q. Ahmed
Jayaprakash Sasikumar
Suparna Laha
Shankar Prasad Das
Publication date: 06-09-2024
Publisher: Springer US
Published in: Cancer and Metastasis Reviews
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-024-10209-3

2024 ESMO Congress

Add-on Ra223 could be a new first-line option in mCRPC

17-09-2024
Prostate Cancer
News

Adding radium-223 to first-line enzalutamide significantly improves the survival of patients with bone metastatic castration-resistant prostate cancer.

19-09-2024
Diagnostics in Oncology
News

No OS benefit of adding preoperative CRT in gastric cancer

17-09-2024
Gastric Cancer
News

T-DXd supported for breast cancer with brain metastases

17-09-2024
Breast Cancer
News

» View more highlights on the ESMO 2024 hub page

Recent advances in the use of CAR T-cell therapies in relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma

Webinar | 01-10-2024 | 12:30 (CEST)

Live event concluded

In this webinar, Professor Martin Dreyling and an esteemed, international panel of CAR-T experts discuss the latest data on the safety, efficacy, and clinical impact of CAR T-cell therapies in the treatment of r/r DLBCL and r/r FL.

Please note, this webinar is not intended for healthcare professionals based in the US and UK.

Keynote webinar | Spotlight on modern management of frailty

Springer Medicine

Multifaceted role of the DNA replication protein MCM10 in maintaining genome stability and its implication in human diseases

Abstract

2024 ESMO Congress

Add-on Ra223 could be a new first-line option in mCRPC

AI model can predict tumor mutations

No OS benefit of adding preoperative CRT in gastric cancer

T-DXd supported for breast cancer with brain metastases

» View more highlights on the ESMO 2024 hub page

Recent advances in the use of CAR T-cell therapies in relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma

Live event concluded

Keynote webinar | Spotlight on modern management of frailty

Springer Medicine

Abstract

Please log in to get access to this content

2024 ESMO Congress

Add-on Ra223 could be a new first-line option in mCRPC

AI model can predict tumor mutations

No OS benefit of adding preoperative CRT in gastric cancer

T-DXd supported for breast cancer with brain metastases

» View more highlights on the ESMO 2024 hub page

Recent advances in the use of CAR T-cell therapies in relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma

Live event concluded