Abstract
Minichromosome maintenance protein 10 (Mcm10) is a conserved component of the eukaryotic DNA replication machinery. Mcm10 promotes the initiation of replication by facilitating DNA unwinding and origin firing. Although the molecular details of this action remain unclear, current data support a scaffolding role for Mcm10 via interactions with DNA and other protein partners. Mcm10 binds both single- and double-stranded DNA, as well as components of the CMG helicase complex, DNA polymerase-α, and Ctf4. Upon initiation, Mcm10 becomes part of the replisome, primarily mediating the initiation of Okazaki fragment synthesis, which involves DNA polymerase-α/primase and the replication clamp PCNA. Mcm10 likely contributes to the recruitment of both of these factors. Emerging concepts predict that steady-state levels of Mcm10 are tightly controlled to balance origin firing and fork progression. Investigations into the cellular requirements for Mcm10 have also revealed a key role in maintaining genome stability. Accordingly, it is not surprising that genetic alterations of MCM10 are associated with cancer. Loss of Mcm10 function is a possible source of DNA damage, whereas overexpression of Mcm10 might serve to facilitate rapid DNA synthesis and proliferation. In this chapter, we provide a comprehensive review of the current literature describing Mcm10’s role in replication initiation. Additionally, we consider how contributions to elongation and other potential functions may affect chromosomal integrity.
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Dumas LB, Lussky JP, McFarland EJ, Shampay J. New temperature-sensitive mutants of Saccharomyces cerevisiae affecting DNA replication. Mol Gen Genet. 1982;187(1):42–6.
Solomon NA, Wright MB, Chang S, Buckley AM, Dumas LB, Gaber RF. Genetic and molecular analysis of DNA43 and DNA52: two new cell-cycle genes in Saccharomyces cerevisiae. Yeast. 1992;8(4):273–89.
Maine GT, Sinha P, Tye BK. Mutants of S. cerevisiae defective in the maintenance of minichromosomes. Genetics. 1984;106(3):365–85.
Merchant AM, Kawasaki Y, Chen Y, Lei M, Tye BK. A lesion in the DNA replication initiation factor Mcm10 induces pausing of elongation forks through chromosomal replication origins in Saccharomyces cerevisiae. Mol Cell Biol. 1997;17(6):3261–71.
Aves SJ, Tongue N, Foster AJ, Hart EA. The essential Schizosaccharomyces pombe cdc23 DNA replication gene shares structural and functional homology with the Saccharomyces cerevisiae DNA43 (MCM10) gene. Curr Genet. 1998;34(3):164–71.
Christensen TW, Tye BK. Drosophila MCM10 interacts with members of the prereplication complex and is required for proper chromosome condensation. Mol Biol Cell. 2003;14(6):2206–15.
Izumi M, Yanagi K, Mizuno T, Yokoi M, Kawasaki Y, Moon KY, et al. The human homolog of Saccharomyces cerevisiae Mcm10 interacts with replication factors and dissociates from nuclease-resistant nuclear structures in G(2) phase. Nucleic Acids Res. 2000;28(23):4769–77.
Lim HJ, Jeon Y, Jeon CH, Kim JH, Lee H. Targeted disruption of Mcm10 causes defective embryonic cell proliferation and early embryo lethality. Biochim Biophys Acta. 2011;1813(10):1777–83.
Wohlschlegel JA, Dhar SK, Prokhorova TA, Dutta A, Walter JC. Xenopus Mcm10 binds to origins of DNA replication after Mcm2-7 and stimulates origin binding of Cdc45. Mol Cell. 2002;9(2):233–40.
Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al. UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem. 2004;25(13):1605–12.
Du W, Josephrajan A, Adhikary S, Bowles T, Bielinsky AK, Eichman BF. Mcm10 self-association is mediated by an N-terminal coiled-coil domain. PLoS One. 2013;8(7):e70518.
Du W, Stauffer ME, Eichman BF. Structural biology of replication initiation factor Mcm10. Subcell Biochem. 2012;62:197–216.
Robertson PD, Warren EM, Zhang H, Friedman DB, Lary JW, Cole JL, et al. Domain architecture and biochemical characterization of vertebrate Mcm10. J Biol Chem. 2008;283(6):3338–48.
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.
Fien K, Cho YS, Lee JK, Raychaudhuri S, Tappin I, Hurwitz J. Primer utilization by DNA polymerase alpha-primase is influenced by its interaction with Mcm10p. J Biol Chem. 2004;279(16):16144–53.
Ricke RM, Bielinsky AK. Mcm10 regulates the stability and chromatin association of DNA polymerase-alpha. Mol Cell. 2004;16(2):173–85.
Ricke RM, Bielinsky AK. A conserved Hsp10-like domain in Mcm10 is required to stabilize the catalytic subunit of DNA polymerase-alpha in budding yeast. J Biol Chem. 2006;281(27):18414–25.
Thu YM, Bielinsky AK. Enigmatic roles of Mcm10 in DNA replication. Trends Biochem Sci. 2013;38(4):184–94.
Warren EM, Huang H, Fanning E, Chazin WJ, Eichman BF. Physical interactions between Mcm10, DNA, and DNA polymerase alpha. J Biol Chem. 2009;284(36):24662–72.
Cook CR, Kung G, Peterson FC, Volkman BF, Lei M. A novel zinc finger is required for Mcm10 homocomplex assembly. J Biol Chem. 2003;278(38):36051–8.
Okorokov AL, Waugh A, Hodgkinson J, Murthy A, Hong HK, Leo E, et al. Hexameric ring structure of human MCM10 DNA replication factor. EMBO Rep. 2007;8(10):925–30.
Warren EM, Vaithiyalingam S, Haworth J, Greer B, Bielinsky AK, Chazin WJ, et al. Structural basis for DNA binding by replication initiator Mcm10. Structure. 2008;16(12):1892–901.
Di Perna R, Aria V, De Falco M, Sannino V, Okorokov AL, Pisani FM, et al. The physical interaction of Mcm10 with Cdc45 modulates their DNA-binding properties. Biochem J. 2013;454(2):333–43.
Robertson PD, Chagot B, Chazin WJ, Eichman BF. Solution NMR structure of the C-terminal DNA binding domain of Mcm10 reveals a conserved MCM motif. J Biol Chem. 2010;285(30):22942–9.
Eisenberg S, Korza G, Carson J, Liachko I, Tye BK. Novel DNA binding properties of the Mcm10 protein from Saccharomyces cerevisiae. J Biol Chem. 2009;284(37):25412–20.
Alver RC, Zhang T, Josephrajan A, Fultz BL, Hendrix CJ, Das-Bradoo S, et al. The N-terminus of Mcm10 is important for interaction with the 9-1-1 clamp and in resistance to DNA damage. Nucleic Acids Res. 2014;42(13):8389–404.
Das-Bradoo S, Ricke RM, Bielinsky AK. Interaction between PCNA and diubiquitinated Mcm10 is essential for cell growth in budding yeast. Mol Cell Biol. 2006;26(13):4806–17.
Dua R, Levy DL, Li CM, Snow PM, Campbell JL. In vivo reconstitution of Saccharomyces cerevisiae DNA polymerase epsilon in insect cells. Purification and characterization. J Biol Chem. 2002;277(10):7889–96.
Schmidt KH, Derry KL, Kolodner RD. Saccharomyces cerevisiae RRM3, a 5′ to 3′ DNA helicase, physically interacts with proliferating cell nuclear antigen. J Biol Chem. 2002;277(47):45331–7.
Vivona JB, Kelman Z. The diverse spectrum of sliding clamp interacting proteins. FEBS Lett. 2003;546(2–3):167–72.
Evrin C, Clarke P, Zech J, Lurz R, Sun J, Uhle S, et al. A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication. Proc Natl Acad Sci U S A. 2009;106(48):20240–5.
Masai H, Matsumoto S, You Z, Yoshizawa-Sugata N, Oda M. Eukaryotic chromosome DNA replication: where, when, and how? Annu Rev Biochem. 2010;79:89–130.
Remus D, Beuron F, Tolun G, Griffith JD, Morris EP, Diffley JF. Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing. Cell. 2009;139(4):719–30.
Bleichert F, Botchan MR, Berger JM. Crystal structure of the eukaryotic origin recognition complex. Nature. 2015;519(7543):321–6.
Ticau S, Friedman LJ, Ivica NA, Gelles J, Bell SP. Single-molecule studies of origin licensing reveal mechanisms ensuring bidirectional helicase loading. Cell. 2015;161(3):513–25.
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.
Sheu YJ, Stillman B. Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression. Mol Cell. 2006;24(1):101–13.
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.
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.
Tanaka T, Umemori T, Endo S, Muramatsu S, Kanemaki M, Kamimura Y, et al. Sld7, an Sld3-associated protein required for efficient chromosomal DNA replication in budding yeast. EMBO J. 2011;30(10):2019–30.
Bochman ML, Schwacha A. The Mcm2-7 complex has in vitro helicase activity. Mol Cell. 2008;31(2):287–93.
Moyer SE, Lewis PW, Botchan MR. Isolation of the Cdc45/Mcm2-7/GINS (CMG) complex, a candidate for the eukaryotic DNA replication fork helicase. Proc Natl Acad Sci U S A. 2006;103(27):10236–41.
Fu YV, Yardimci H, Long DT, Ho TV, Guainazzi A, Bermudez VP, et al. Selective bypass of a lagging strand roadblock by the eukaryotic replicative DNA helicase. Cell. 2011;146(6):931–41.
Sun J, Fernandez-Cid A, Riera A, Tognetti S, Yuan Z, Stillman B, et al. Structural and mechanistic insights into Mcm2-7 double-hexamer assembly and function. Genes Dev. 2014;28(20):2291–303.
Bruck I, Kaplan DL. The Dbf4-Cdc7 kinase promotes Mcm2-7 ring opening to allow for single-stranded DNA extrusion and helicase assembly. J Biol Chem. 2015;290(2):1210–21.
Hart EA, Bryant JA, Moore K, Aves SJ. Fission yeast Cdc23 interactions with DNA replication initiation proteins. Curr Genet. 2002;41(5):342–8.
Homesley L, Lei M, Kawasaki Y, Sawyer S, Christensen T, Tye BK. Mcm10 and the MCM2-7 complex interact to initiate DNA synthesis and to release replication factors from origins. Genes Dev. 2000;14(8):913–26.
Lee JK, Seo YS, Hurwitz J. The Cdc23 (Mcm10) protein is required for the phosphorylation of minichromosome maintenance complex by the Dfp1-Hsk1 kinase. Proc Natl Acad Sci U S A. 2003;100(5):2334–9.
Sawyer SL, Cheng IH, Chai W, Tye BK. Mcm10 and Cdc45 cooperate in origin activation in Saccharomyces cerevisiae. J Mol Biol. 2004;340(2):195–202.
Kawasaki Y, Hiraga S, Sugino A. Interactions between Mcm10p and other replication factors are required for proper initiation and elongation of chromosomal DNA replication in Saccharomyces cerevisiae. Genes Cells. 2000;5(12):975–89.
Xu X, Rochette PJ, Feyissa EA, Su TV, Liu Y. MCM10 mediates RECQ4 association with MCM2-7 helicase complex during DNA replication. EMBO J. 2009;28(19):3005–14.
Araki Y, Kawasaki Y, Sasanuma H, Tye BK, Sugino A. Budding yeast mcm10/dna43 mutant requires a novel repair pathway for viability. Genes Cells. 2003;8(5):465–80.
Izumi M, Yatagai F, Hanaoka F. Cell cycle-dependent proteolysis and phosphorylation of human Mcm10. J Biol Chem. 2001;276(51):48526–31.
Kaur M, Sharma A, Khan M, Kar A, Saxena S. Mcm10 proteolysis initiates before the onset of M-phase. BMC Cell Biol. 2010;11:84.
Sharma A, Kaur M, Kar A, Ranade SM, Saxena S. Ultraviolet radiation stress triggers the down-regulation of essential replication factor Mcm10. J Biol Chem. 2010;285(11):8352–62.
Lan W, Chen S, Tong L. MicroRNA-215 regulates fibroblast function: insights from a human fibrotic disease. Cell Cycle. 2015;14(12):1973–84.
Yoshida K, Inoue I. Expression of MCM10 and TopBP1 is regulated by cell proliferation and UV irradiation via the E2F transcription factor. Oncogene. 2004;23(37):6250–60.
Watase G, Takisawa H, Kanemaki MT. Mcm10 plays a role in functioning of the eukaryotic replicative DNA helicase, Cdc45-Mcm-GINS. Curr Biol. 2012;22(4):343–9.
Gambus A, van Deursen F, Polychronopoulos D, Foltman M, Jones RC, Edmondson RD, et al. A key role for Ctf4 in coupling the MCM2-7 helicase to DNA polymerase alpha within the eukaryotic replisome. EMBO J. 2009;28(19):2992–3004.
Gregan J, Lindner K, Brimage L, Franklin R, Namdar M, Hart EA, et al. Fission yeast Cdc23/Mcm10 functions after pre-replicative complex formation to promote Cdc45 chromatin binding. Mol Biol Cell. 2003;14(9):3876–87.
Heller RC, Kang S, Lam WM, Chen S, Chan CS, Bell SP. Eukaryotic origin-dependent DNA replication in vitro reveals sequential action of DDK and S-CDK kinases. Cell. 2011;146(1):80–91.
Im JS, Ki SH, Farina A, Jung DS, Hurwitz J, Lee JK. Assembly of the Cdc45-Mcm2-7-GINS complex in human cells requires the Ctf4/And-1, RecQL4, and Mcm10 proteins. Proc Natl Acad Sci U S A. 2009;106(37):15628–32.
Im JS, Park SY, Cho WH, Bae SH, Hurwitz J, Lee JK. RecQL4 is required for the association of Mcm10 and Ctf4 with replication origins in human cells. Cell Cycle. 2015;14(7):1001–9.
On KF, Beuron F, Frith D, Snijders AP, Morris EP, Diffley JF. Prereplicative complexes assembled in vitro support origin-dependent and independent DNA replication. EMBO J. 2014;33(6):605–20.
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.
Donovan S, Harwood J, Drury LS, Diffley JF. Cdc6p-dependent loading of Mcm proteins onto pre-replicative chromatin in budding yeast. Proc Natl Acad Sci U S A. 1997;94(11):5611–6.
Edwards MC, Tutter AV, Cvetic C, Gilbert CH, Prokhorova TA, Walter JC. MCM2-7 complexes bind chromatin in a distributed pattern surrounding the origin recognition complex in Xenopus egg extracts. J Biol Chem. 2002;277(36):33049–57.
Lei M, Kawasaki Y, Tye BK. Physical interactions among Mcm proteins and effects of Mcm dosage on DNA replication in Saccharomyces cerevisiae. Mol Cell Biol. 1996;16(9):5081–90.
Mahbubani HM, Chong JP, Chevalier S, Thommes P, Blow JJ. Cell cycle regulation of the replication licensing system: involvement of a Cdk-dependent inhibitor. J Cell Biol. 1997;136(1):125–35.
Kanke M, Kodama Y, Takahashi TS, Nakagawa T, Masukata H. Mcm10 plays an essential role in origin DNA unwinding after loading of the CMG components. EMBO J. 2012;31(9):2182–94.
van Deursen F, Sengupta S, De Piccoli G, Sanchez-Diaz A, Labib K. Mcm10 associates with the loaded DNA helicase at replication origins and defines a novel step in its activation. EMBO J. 2012;31(9):2195–206.
Yu C, Gan H, Han J, Zhou ZX, Jia S, Chabes A, et al. Strand-specific analysis shows protein binding at replication forks and PCNA unloading from lagging strands when forks stall. Mol Cell. 2014;56(4):551–63.
Zhu W, Ukomadu C, Jha S, Senga T, Dhar SK, Wohlschlegel JA, et al. Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication. Genes Dev. 2007;21(18):2288–99.
Yang X, Gregan J, Lindner K, Young H, Kearsey SE. Nuclear distribution and chromatin association of DNA polymerase alpha-primase is affected by TEV protease cleavage of Cdc23 (Mcm10) in fission yeast. BMC Mol Biol. 2005;6:13.
Kunkel TA, Burgers PM. Dividing the workload at a eukaryotic replication fork. Trends Cell Biol. 2008;18(11):521–7.
Nick McElhinny SA, Gordenin DA, Stith CM, Burgers PM, Kunkel TA. Division of labor at the eukaryotic replication fork. Mol Cell. 2008;30(2):137–44.
Pacek M, Tutter AV, Kubota Y, Takisawa H, Walter JC. Localization of MCM2-7, Cdc45, and GINS to the site of DNA unwinding during eukaryotic DNA replication. Mol Cell. 2006;21(4):581–7.
Alabert C, Bukowski-Wills JC, Lee SB, Kustatscher G, Nakamura K, de Lima Alves F, et al. Nascent chromatin capture proteomics determines chromatin dynamics during DNA replication and identifies unknown fork components. Nat Cell Biol. 2014;16(3):281–93.
Aparicio OM, Weinstein DM, Bell SP. Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase. Cell. 1997;91(1):59–69.
Taylor M, Moore K, Murray J, Aves SJ, Price C. Mcm10 interacts with Rad4/Cut5(TopBP1) and its association with origins of DNA replication is dependent on Rad4/Cut5(TopBP1). DNA Repair (Amst). 2011;10(11):1154–63.
Nasheuer HP, Grosse F. Immunoaffinity-purified DNA polymerase alpha displays novel properties. Biochemistry. 1987;26(25):8458–66.
Kouprina N, Kroll E, Bannikov V, Bliskovsky V, Gizatullin R, Kirillov A, et al. CTF4 (CHL15) mutants exhibit defective DNA metabolism in the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1992;12(12):5736–47.
Apger J, Reubens M, Henderson L, Gouge CA, Ilic N, Zhou HH, et al. Multiple functions for Drosophila Mcm10 suggested through analysis of two Mcm10 mutant alleles. Genetics. 2010;185(4):1151–65.
Gosnell JA, Christensen TW. Drosophila Ctf4 is essential for efficient DNA replication and normal cell cycle progression. BMC Mol Biol. 2011;12:13.
Chattopadhyay S, Bielinsky AK. Human Mcm10 regulates the catalytic subunit of DNA polymerase-alpha and prevents DNA damage during replication. Mol Biol Cell. 2007;18(10):4085–95.
Haworth J, Alver RC, Anderson M, Bielinsky AK. Ubc4 and Not4 regulate steady-state levels of DNA polymerase-alpha to promote efficient and accurate DNA replication. Mol Biol Cell. 2010;21(18):3205–19.
Lee C, Liachko I, Bouten R, Kelman Z, Tye BK. Alternative mechanisms for coordinating polymerase alpha and MCM helicase. Mol Cell Biol. 2010;30(2):423–35.
Wang J, Wu R, Lu Y, Liang C. Ctf4p facilitates Mcm10p to promote DNA replication in budding yeast. Biochem Biophys Res Commun. 2010;395(3):336–41.
Wawrousek KE, Fortini BK, Polaczek P, Chen L, Liu Q, Dunphy WG, et al. Xenopus DNA2 is a helicase/nuclease that is found in complexes with replication proteins And-1/Ctf4 and Mcm10 and DSB response proteins Nbs1 and ATM. Cell Cycle. 2010;9(6):1156–66.
Simon AC, Zhou JC, Perera RL, van Deursen F, Evrin C, Ivanova ME, et al. A Ctf4 trimer couples the CMG helicase to DNA polymerase alpha in the eukaryotic replisome. Nature. 2014;510(7504):293–7.
Fumasoni M, Zwicky K, Vanoli F, Lopes M, Branzei D. Error-free DNA damage tolerance and sister chromatid proximity during DNA replication rely on the Polalpha/Primase/Ctf4 complex. Mol Cell. 2015;57(5):812–23.
Kim S, Dallmann HG, McHenry CS, Marians KJ. tau couples the leading- and lagging-strand polymerases at the Escherichia coli DNA replication fork. J Biol Chem. 1996;271(35):21406–12.
Kim S, Dallmann HG, McHenry CS, Marians KJ. Coupling of a replicative polymerase and helicase: a tau-DnaB interaction mediates rapid replication fork movement. Cell. 1996;84(4):643–50.
Kurth I, O’Donnell M. New insights into replisome fluidity during chromosome replication. Trends Biochem Sci. 2013;38(4):195–203.
Dalrymple BP, Kongsuwan K, Wijffels G, Dixon NE, Jennings PA. A universal protein-protein interaction motif in the eubacterial DNA replication and repair systems. Proc Natl Acad Sci U S A. 2001;98(20):11627–32.
Thu YM, Bielinsky AK. MCM10: one tool for all-Integrity, maintenance and damage control. Semin Cell Dev Biol. 2014;30:121–30.
Ellison V, Stillman B. Biochemical characterization of DNA damage checkpoint complexes: clamp loader and clamp complexes with specificity for 5′ recessed DNA. PLoS Biol. 2003;1(2):E33.
Majka J, Binz SK, Wold MS, Burgers PM. Replication protein A directs loading of the DNA damage checkpoint clamp to 5′-DNA junctions. J Biol Chem. 2006;281(38):27855–61.
Becker JR, Nguyen HD, Wang X, Bielinsky AK. Mcm10 deficiency causes defective-replisome-induced mutagenesis and a dependency on error-free postreplicative repair. Cell Cycle. 2014;13(11):1737–48.
Miotto B, Chibi M, Xie P, Koundrioukoff S, Moolman-Smook H, Pugh D, et al. The RBBP6/ZBTB38/MCM10 axis regulates DNA replication and common fragile site stability. Cell Rep. 2014;7(2):575–87.
Davies SL, North PS, Hickson ID. Role for BLM in replication-fork restart and suppression of origin firing after replicative stress. Nat Struct Mol Biol. 2007;14(7):677–9.
Rosenberg C, Florijn RJ, Van de Rijke FM, Blonden LA, Raap TK, Van Ommen GJ, et al. High resolution DNA fiber-fish on yeast artificial chromosomes: direct visualization of DNA replication. Nat Genet. 1995;10(4):477–9.
Kawabata T, Luebben SW, Yamaguchi S, Ilves I, Matise I, Buske T, et al. Stalled fork rescue via dormant replication origins in unchallenged S phase promotes proper chromosome segregation and tumor suppression. Mol Cell. 2011;41(5):543–53.
Woodward AM, Gohler T, Luciani MG, Oehlmann M, Ge X, Gartner A, et al. Excess Mcm2-7 license dormant origins of replication that can be used under conditions of replicative stress. J Cell Biol. 2006;173(5):673–83.
Lukas C, Savic V, Bekker-Jensen S, Doil C, Neumann B, Pedersen RS, et al. 53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress. Nat Cell Biol. 2011;13(3):243–53.
Paulsen RD, Soni DV, Wollman R, Hahn AT, Yee MC, Guan A, et al. A genome-wide siRNA screen reveals diverse cellular processes and pathways that mediate genome stability. Mol Cell. 2009;35(2):228–39.
Park JH, Bang SW, Jeon Y, Kang S, Hwang DS. Knockdown of human MCM10 exhibits delayed and incomplete chromosome replication. Biochem Biophys Res Commun. 2008;365(3):575–82.
Park JH, Bang SW, Kim SH, Hwang DS. Knockdown of human MCM10 activates G2 checkpoint pathway. Biochem Biophys Res Commun. 2008;365(3):490–5.
Tittel-Elmer M, Alabert C, Pasero P, Cobb JA. The MRX complex stabilizes the replisome independently of the S phase checkpoint during replication stress. EMBO J. 2009;28(8):1142–56.
Wu C, Zhu J, Zhang X. Integrating gene expression and protein-protein interaction network to prioritize cancer-associated genes. BMC Bioinformatics. 2012;13:182.
Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2(5):401–4.
Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6(269):l1.
Kang G, Hwang WC, Do IG, Wang K, Kang SY, Lee J, et al. Exome sequencing identifies early gastric carcinoma as an early stage of advanced gastric cancer. PLoS One. 2013;8(12):e82770.
Halazonetis TD, Gorgoulis VG, Bartek J. An oncogene-induced DNA damage model for cancer development. Science. 2008;319(5868):1352–5.
Burrell RA, McClelland SE, Endesfelder D, Groth P, Weller MC, Shaikh N, et al. Replication stress links structural and numerical cancer chromosomal instability. Nature. 2013;494(7438):492–6.
Garcia-Aragoncillo E, Carrillo J, Lalli E, Agra N, Gomez-Lopez G, Pestana A, et al. DAX1, a direct target of EWS/FLI1 oncoprotein, is a principal regulator of cell-cycle progression in Ewing’s tumor cells. Oncogene. 2008;27(46):6034–43.
Koppen A, Ait-Aissa R, Koster J, van Sluis PG, Ora I, Caron HN, et al. Direct regulation of the minichromosome maintenance complex by MYCN in neuroblastoma. Eur J Cancer. 2007;43(16):2413–22.
Das M, Prasad SB, Yadav SS, Govardhan HB, Pandey LK, Singh S, et al. Over expression of minichromosome maintenance genes is clinically correlated to cervical carcinogenesis. PLoS One. 2013;8(7):e69607.
Nijhawan D, Zack TI, Ren Y, Strickland MR, Lamothe R, Schumacher SE, et al. Cancer vulnerabilities unveiled by genomic loss. Cell. 2012;150(4):842–54.
Liachko I, Tye BK. Mcm10 is required for the maintenance of transcriptional silencing in Saccharomyces cerevisiae. Genetics. 2005;171(2):503–15.
Liachko I, Tye BK. Mcm10 mediates the interaction between DNA replication and silencing machineries. Genetics. 2009;181(2):379–91.
Vo N, Taga A, Inaba Y, Yoshida H, Cotterill S, Yamaguchi M. Drosophila Mcm10 is required for DNA replication and differentiation in the compound eye. PLoS One. 2014; 9(3):e93450.
Wang JT, Xu X, Alontaga AY, Chen Y, Liu Y. Impaired p32 regulation caused by the lymphoma-prone RECQ4 mutation drives mitochondrial dysfunction. Cell Rep. 2014;7(3):848–58.
Acknowledgements
The authors wish to acknowledge funding from the National Institutes of Health R01 GM074917 to A.K.B. R.M.B. was supported by Cancer Biology Training Grant NIH T32 CA009138.
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Baxley, R.M., Thu, Y.M., Bielinsky, AK. (2016). The Role of Mcm10 in Replication Initiation. In: Kaplan, D. (eds) The Initiation of DNA Replication in Eukaryotes. Springer, Cham. https://doi.org/10.1007/978-3-319-24696-3_16
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