Genomes and Genes
Gene Symbol: MCM3
Description: MCM DNA helicase complex subunit MCM3
Alias: MCM DNA helicase complex subunit MCM3
Species: Saccharomyces cerevisiae S288c
- Sengupta S, van Deursen F, De Piccoli G, Labib K. Dpb2 integrates the leading-strand DNA polymerase into the eukaryotic replisome. Curr Biol. 2013;23:543-52 pubmed publisher..Second, it plays an equally important role after initiation, because it links the leading strand DNA polymerase to the Cdc45-MCM-GINS helicase within the replisome. ..
- 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;106:20240-5 pubmed publisher..Our results provide key insights into mechanisms of pre-RC formation and have important implications for understanding the role of the MCM2-7 in establishment of bidirectional replication forks. ..
- Sun J, Evrin C, Samel S, Fernández Cid A, Riera A, Kawakami H, et al. Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA. Nat Struct Mol Biol. 2013;20:944-51 pubmed publisher..The resulting ORC-Cdc6 helicase loader shows a notable structural similarity to the replication factor C clamp loader, suggesting a conserved mechanism of action. ..
- Bruck I, Kanter D, Kaplan D. Enabling association of the GINS protein tetramer with the mini chromosome maintenance (Mcm)2-7 protein complex by phosphorylated Sld2 protein and single-stranded origin DNA. J Biol Chem. 2011;286:36414-26 pubmed publisher..Furthermore, origin ssDNA may stimulate the formation of the CMG complex by alleviating inhibitory interactions between Sld2 with Mcm2-7. ..
- GarcÃa RodrÃguez L, De Piccoli G, Marchesi V, Jones R, Edmondson R, Labib K. A conserved PolÏµ binding module in Ctf18-RFC is required for S-phase checkpoint activation downstream of Mec1. Nucleic Acids Res. 2015;43:8830-8 pubmed publisher..These findings indicate that the association of Ctf18-RFC with Pol Ïµ at defective replication forks is a key step in activation of the S-phase checkpoint. ..
- Langston L, Mayle R, Schauer G, Yurieva O, Zhang D, Yao N, et al. Mcm10 promotes rapid isomerization of CMG-DNA for replisome bypass of lagging strand DNA blocks. elife. 2017;6: pubmed publisher..We demonstrate that bypass occurs without displacement of the blocks and therefore Mcm10 must isomerize the CMG-DNA complex to achieve the bypass function. ..
- Loog M, Morgan D. Cyclin specificity in the phosphorylation of cyclin-dependent kinase substrates. Nature. 2005;434:104-8 pubmed..The Clb5-specific targets include several proteins (Sld2, Cdc6, Orc6, Mcm3 and Cdh1) involved in early S-phase events...
- Bruck I, Kaplan D. GINS and Sld3 compete with one another for Mcm2-7 and Cdc45 binding. J Biol Chem. 2011;286:14157-67 pubmed publisher..Our results are consistent with a model wherein GINS trades places with Sld3 at a replication origin, contributing to the activation of the replication fork helicase. ..
- Komata M, Bando M, Araki H, Shirahige K. The direct binding of Mrc1, a checkpoint mediator, to Mcm6, a replication helicase, is essential for the replication checkpoint against methyl methanesulfonate-induced stress. Mol Cell Biol. 2009;29:5008-19 pubmed publisher..These results strongly suggest for the first time that an Mcm helicase acts as a checkpoint sensor for methyl methanesulfonate-induced DNA damage through direct binding to the replication checkpoint mediator Mrc1. ..
- Ma L, Zhai Y, Feng D, Chan T, Lu Y, Fu X, et al. Identification of novel factors involved in or regulating initiation of DNA replication by a genome-wide phenotypic screen in Saccharomyces cerevisiae. Cell Cycle. 2010;9:4399-410 pubmed..These data suggest that Ctf1p and Ctf18p together play important roles in regulating the initiation of DNA replication. ..
- Lydeard J, Lipkin Moore Z, Sheu Y, Stillman B, Burgers P, Haber J. Break-induced replication requires all essential DNA replication factors except those specific for pre-RC assembly. Genes Dev. 2010;24:1133-44 pubmed publisher..These results suggest that origin-independent BIR involves cross-talk between normal DNA replication factors and PRR. ..
- Yuan Z, Riera A, Bai L, Sun J, Nandi S, Spanos C, et al. Structural basis of Mcm2-7 replicative helicase loading by ORC-Cdc6 and Cdt1. Nat Struct Mol Biol. 2017;24:316-324 pubmed publisher..This structure suggests a loading mechanism of the first Cdt1-bound Mcm2-7 hexamer by ORC-Cdc6. ..
- Liku M, Nguyen V, Rosales A, Irie K, Li J. CDK phosphorylation of a novel NLS-NES module distributed between two subunits of the Mcm2-7 complex prevents chromosomal rereplication. Mol Biol Cell. 2005;16:5026-39 pubmed..Here we identify two partial nuclear localization signals (NLSs) on Mcm2 and Mcm3 that are each necessary, but not sufficient, for nuclear localization of the Mcm2-7 complex...
- Wilmes G, Bell S. The B2 element of the Saccharomyces cerevisiae ARS1 origin of replication requires specific sequences to facilitate pre-RC formation. Proc Natl Acad Sci U S A. 2002;99:101-6 pubmed..The function of these mutant sequences is rescued by Cdc6p overexpression. We propose that the B2 element requires specific sequences to bind a component of the pre-RC. ..
- Garber P, Rine J. Overlapping roles of the spindle assembly and DNA damage checkpoints in the cell-cycle response to altered chromosomes in Saccharomyces cerevisiae. Genetics. 2002;161:521-34 pubmed..Thus the specificity of this checkpoint may be more limited than previously recognized. ..
- Yan H, Merchant A, Tye B. Cell cycle-regulated nuclear localization of MCM2 and MCM3, which are required for the initiation of DNA synthesis at chromosomal replication origins in yeast. Genes Dev. 1993;7:2149-60 pubmedMCM2 and MCM3 are two genetically interacting and structurally related proteins essential for growth in Saccharomyces cerevisiae...
- Sheu Y, Stillman B. Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression. Mol Cell. 2006;24:101-13 pubmed..We suggest that DDK docks on and phosphorylates MCM proteins at licensed origins to promote proper assembly of pre-IC. ..
- Weinreich M, Stillman B. Cdc7p-Dbf4p kinase binds to chromatin during S phase and is regulated by both the APC and the RAD53 checkpoint pathway. EMBO J. 1999;18:5334-46 pubmed..Cdc7p-Dbf4p efficiently phosphorylates several proteins that are required for the initiation of DNA replication, including five of the six Mcm proteins and the p180 subunit of DNA polymerase alpha-primase. ..
- Lei M, Cheng I, Roberts L, McAlear M, Tye B. Two mcm3 mutations affect different steps in the initiation of DNA replication. J Biol Chem. 2002;277:30824-31 pubmedb>Mcm3 is a subunit of the hexameric MCM2-7 complex required for the initiation and elongation of DNA replication in eukaryotes...
- Samel S, Fernández Cid A, Sun J, Riera A, Tognetti S, Herrera M, et al. A unique DNA entry gate serves for regulated loading of the eukaryotic replicative helicase MCM2-7 onto DNA. Genes Dev. 2014;28:1653-66 pubmed publisher..Our study establishes the existence of a unique DNA entry gate for regulated helicase loading, revealing key mechanisms in helicase loading, which has important implications for helicase activation. ..
- Yan H, Gibson S, Tye B. Mcm2 and Mcm3, two proteins important for ARS activity, are related in structure and function. Genes Dev. 1991;5:944-57 pubmedMCM2 and MCM3 are essential genes believed to play important roles in the initiation of DNA replication in Saccharomyces cerevisiae. Mutants defective in Mcm2 or Mcm3 are remarkably similar in phenotype...
- Evrin C, Fernández Cid A, Riera A, Zech J, Clarke P, Herrera M, et al. The ORC/Cdc6/MCM2-7 complex facilitates MCM2-7 dimerization during prereplicative complex formation. Nucleic Acids Res. 2014;42:2257-69 pubmed publisher..Our work identifies the OCM complex as competent for MCM2-7 dimerization, reveals MCM2-7 dimerization as a limiting step during pre-RC formation and defines critical mechanisms that explain how origins are licensed. ..
- Merchant A, Kawasaki Y, Chen Y, Lei M, Tye B. 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;17:3261-71 pubmed..This novel phenotype suggests a unique role for the Mcm10 protein in the initiation of DNA synthesis at replication origins. ..
- Wysocka M, Rytka J, Kurlandzka A. Saccharomyces cerevisiae CSM1 gene encoding a protein influencing chromosome segregation in meiosis I interacts with elements of the DNA replication complex. Exp Cell Res. 2004;294:592-602 pubmed..The Csm1p-Mcm3, Mcm5 and Mcm7p interactions were confirmed by co-immunoprecipitation...
- Froelich C, Kang S, Epling L, Bell S, Enemark E. A conserved MCM single-stranded DNA binding element is essential for replication initiation. elife. 2014;3:e01993 pubmed publisher..Our findings identify an important MCM-ssDNA interaction and suggest it functions during helicase activation to select the strand for translocation. DOI: http://dx.doi.org/10.7554/eLife.01993.001...
- Nedelcheva M, Roguev A, Dolapchiev L, Shevchenko A, Taskov H, Shevchenko A, et al. Uncoupling of unwinding from DNA synthesis implies regulation of MCM helicase by Tof1/Mrc1/Csm3 checkpoint complex. J Mol Biol. 2005;347:509-21 pubmed..In concordance with this suggestion, we found that the Tof1/Csm3/Mrc1 checkpoint complex interacts directly with the MCM helicase during both replication fork progression and when the replication fork is stalled. ..
- Pérez Arnaiz P, Bruck I, Colbert M, Kaplan D. An intact Mcm10 coiled-coil interaction surface is important for origin melting, helicase assembly and the recruitment of Pol-? to Mcm2-7. Nucleic Acids Res. 2017;45:7261-7275 pubmed publisher..We also detected diminished GINS and pol-? recruitment to the Mcm2-7 complex. We conclude that an intact Mcm10 coiled-coil interaction surface is important for origin melting, helicase assembly, and the recruitment of pol ? to Mcm2-7. ..
- Huo L, Wu R, Yu Z, Zhai Y, Yang X, Chan T, et al. The Rix1 (Ipi1p-2p-3p) complex is a critical determinant of DNA replication licensing independent of their roles in ribosome biogenesis. Cell Cycle. 2012;11:1325-39 pubmed publisher..These results establish a new framework for the hierarchy of pre-RC proteins, where the Ipi1p-2p-3p complex provides a critical link between ORC-Noc3p and Cdc6p-Cdt1p-MCM in replication licensing. ..
- Lei M, Kawasaki Y, Young M, Kihara M, Sugino A, Tye B. Mcm2 is a target of regulation by Cdc7-Dbf4 during the initiation of DNA synthesis. Genes Dev. 1997;11:3365-74 pubmed..Taken together, our data suggest that phosphorylation of Mcm2 and probably other members of the Mcm2-7 proteins by Cdc7-Dbf4 at the G1-to-S phase transition is a critical step in the initiation of DNA synthesis at replication origins. ..
- Aparicio O, Weinstein D, Bell S. Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase. Cell. 1997;91:59-69 pubmed..Our results identify protein components of the pre-RC and a novel replication complex appearing at the G1/S transition (the RC), and suggest that after initiation MCM proteins and Cdc45p move with eukaryotic replication forks. ..
- Labib K, Kearsey S, Diffley J. MCM2-7 proteins are essential components of prereplicative complexes that accumulate cooperatively in the nucleus during G1-phase and are required to establish, but not maintain, the S-phase checkpoint. Mol Biol Cell. 2001;12:3658-67 pubmed..Our data indicate that pre-RCs do not play a direct role in checkpoint control during chromosome replication. ..
- Wu R, Wang J, Liang C. Cdt1p, through its interaction with Mcm6p, is required for the formation, nuclear accumulation and chromatin loading of the MCM complex. J Cell Sci. 2012;125:209-19 pubmed publisher..Our findings suggest a function for Cdt1p in promoting the assembly of the MCM complex and maintaining its integrity by interacting with Mcm6p. ..
- Dalton S, Hopwood B. Characterization of Cdc47p-minichromosome maintenance complexes in Saccharomyces cerevisiae: identification of Cdc45p as a subunit. Mol Cell Biol. 1997;17:5867-75 pubmed..This argues that assembly of Cdc47p into complexes with other MCM polypeptides is important for its role in the initiation of chromosomal DNA replication. ..
- Douglas M, Diffley J. Recruitment of Mcm10 to Sites of Replication Initiation Requires Direct Binding to the Minichromosome Maintenance (MCM) Complex. J Biol Chem. 2016;291:5879-88 pubmed publisher..These findings indicate that Mcm10 is localized to replication initiation sites by directly binding MCM through the Mcm10 C terminus. ..
- Quan Y, Xia Y, Liu L, Cui J, Li Z, Cao Q, et al. Cell-Cycle-Regulated Interaction between Mcm10 and Double Hexameric Mcm2-7 Is Required for Helicase Splitting and Activation during S Phase. Cell Rep. 2015;13:2576-2586 pubmed publisher..Therefore, we propose an essential role for Mcm10 in Mcm2-7 remodeling through formation of a cell-cycle-regulated supercomplex with DHs. ..
- Langston L, Zhang D, Yurieva O, Georgescu R, Finkelstein J, Yao N, et al. CMG helicase and DNA polymerase Îµ form a functional 15-subunit holoenzyme for eukaryotic leading-strand DNA replication. Proc Natl Acad Sci U S A. 2014;111:15390-5 pubmed publisher..Direct binding between Pol Îµ and CMG provides an explanation for specific targeting of Pol Îµ to the leading strand and provides clear mechanistic evidence for how strand asymmetry is maintained in eukaryotes. ..
- Dhingra N, Bruck I, Smith S, Ning B, Kaplan D. Dpb11 protein helps control assembly of the Cdc45Â·Mcm2-7Â·GINS replication fork helicase. J Biol Chem. 2015;290:7586-601 pubmed publisher..Finally, we propose that Dpb11 functions with Sld2 and Sld3 to help control the assembly of the replication fork helicase. ..
- Nguyen V, Co C, Irie K, Li J. Clb/Cdc28 kinases promote nuclear export of the replication initiator proteins Mcm2-7. Curr Biol. 2000;10:195-205 pubmed..Such an arrangement could ensure that Mcm proteins complete their replication function before they are removed from the nucleus. ..
- Bruck I, Kaplan D. Conserved mechanism for coordinating replication fork helicase assembly with phosphorylation of the helicase. Proc Natl Acad Sci U S A. 2015;112:11223-8 pubmed publisher..These data suggest a conserved mechanism for replication initiation: Sld3/Treslin coordinates Cdc45 recruitment to Mcm2-7 with DDK phosphorylation of Mcm2 during S phase. ..
- Hardy C. Identification of Cdc45p, an essential factor required for DNA replication. Gene. 1997;187:239-46 pubmed..interacts genetically with ORC2, the gene encoding the second subunit of the origin recognition complex, ORC, and MCM3, another member of the MCM family...
- Cheng I, Roberts L, Tye B. Mcm3 is polyubiquitinated during mitosis before establishment of the pre-replication complex. J Biol Chem. 2002;277:41706-14 pubmed..Reducing the rate of ubiquitination by uba1-165, a suppressor of mcm3-10, restored the interaction of Mcm3-10p with subunits of the MCM complex and its recruitment to the replication ..
- Lei M, Kawasaki Y, Tye B. Physical interactions among Mcm proteins and effects of Mcm dosage on DNA replication in Saccharomyces cerevisiae. Mol Cell Biol. 1996;16:5081-90 pubmedMcm2, Mcm3, and Mcm5/Cdc46 are conserved proteins essential for the initiation of DNA synthesis at replication origins in Saccharomyces cerevisiae...
- Maculins T, Nkosi P, Nishikawa H, Labib K. Tethering of SCF(Dia2) to the Replisome Promotes Efficient Ubiquitylation and Disassembly of the CMG Helicase. Curr Biol. 2015;25:2254-9 pubmed publisher..Residual ubiquitylation of Mcm7 in dia2-Î”TPR cells is still CMG specific, highlighting the complex regulation of the final stages of chromosome replication, about which much still remains to be learned. ..
- Tsai F, Vijayraghavan S, Prinz J, MacAlpine H, MacAlpine D, Schwacha A. Mcm2-7 Is an Active Player in the DNA Replication Checkpoint Signaling Cascade via Proposed Modulation of Its DNA Gate. Mol Cell Biol. 2015;35:2131-43 pubmed publisher..We infer that this conformational change is required for its DRC role and propose that it allosterically facilitates Rad53 activation to ensure a replication-specific checkpoint response. ..
- 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;31:2195-206 pubmed publisher..These findings indicate that Mcm10 is required for a novel step during activation of the Cdc45-MCM-GINS helicase at DNA replication origins. ..
- Bruck I, Kaplan D. Origin single-stranded DNA releases Sld3 protein from the Mcm2-7 complex, allowing the GINS tetramer to bind the Mcm2-7 complex. J Biol Chem. 2011;286:18602-13 pubmed publisher..We also show that origin single-stranded DNA promotes the formation of the CMG complex. We conclude that origin single-stranded DNA releases Sld3 from Mcm2-7, allowing GINS to bind Mcm2-7. ..
- Zou L, Mitchell J, Stillman B. CDC45, a novel yeast gene that functions with the origin recognition complex and Mcm proteins in initiation of DNA replication. Mol Cell Biol. 1997;17:553-63 pubmed..characterization of the cdc45-1 mutant demonstrated that it is synthetically lethal with orc2-1, mcm2-1, and mcm3-1...
- Sun J, Shi Y, Georgescu R, Yuan Z, Chait B, Li H, et al. The architecture of a eukaryotic replisome. Nat Struct Mol Biol. 2015;22:976-82 pubmed publisher..Our work reveals an unexpected configuration of the eukaryotic replisome, suggests possible reasons for this architecture and provides a basis for further structural and biochemical replisome studies. ..
- Deegan T, Yeeles J, Diffley J. Phosphopeptide binding by Sld3 links Dbf4-dependent kinase to MCM replicative helicase activation. EMBO J. 2016;35:961-73 pubmed publisher..Thus, Sld3 is an essential "reader" of DDK phosphorylation, integrating signals from three distinct protein kinase pathways to coordinate DNA replication during S phase. ..
- Villa F, Simon A, Ortiz Bazan M, Kilkenny M, Wirthensohn D, Wightman M, et al. Ctf4 Is a Hub in the Eukaryotic Replisome that Links Multiple CIP-Box Proteins to the CMG Helicase. Mol Cell. 2016;63:385-96 pubmed publisher..Most strikingly, Ctf4-dependent recruitment of CIP-box proteins couples other processes to DNA synthesis, including rDNA copy-number regulation. ..
- Liachko I, Tye B. Mcm10 mediates the interaction between DNA replication and silencing machineries. Genetics. 2009;181:379-91 pubmed publisher..In this study we show that members of the replicative helicase (Mcm3 and Mcm7) play a role in silencing and physically interact with the essential silencing factor, Sir2, even in the ..
- Maric M, Maculins T, De Piccoli G, Labib K. Cdc48 and a ubiquitin ligase drive disassembly of the CMG helicase at the end of DNA replication. Science. 2014;346:1253596 pubmed publisher..These findings indicate that the end of chromosome replication in eukaryotes is controlled in a similarly complex fashion to the much-better-characterized initiation step. ..
- Simon A, Zhou J, Perera R, van Deursen F, Evrin C, Ivanova M, et al. A Ctf4 trimer couples the CMG helicase to DNA polymerase Î± in the eukaryotic replisome. Nature. 2014;510:293-297 pubmed publisher..The ability of Ctf4 to act as a platform for multivalent interactions illustrates a mechanism for the concurrent recruitment of factors that act together at the fork. ..
- Bruck I, Kaplan D. Dbf4-Cdc7 phosphorylation of Mcm2 is required for cell growth. J Biol Chem. 2009;284:28823-31 pubmed publisher..We conclude that DDK phosphorylation of Mcm2 is required for cell growth. ..
- Ramer M, Suman E, Richter H, Stanger K, Spranger M, Bieberstein N, et al. Dbf4 and Cdc7 proteins promote DNA replication through interactions with distinct Mcm2-7 protein subunits. J Biol Chem. 2013;288:14926-35 pubmed publisher..Finally, constitutive overexpression of each individual MCM subunit was examined, and genotoxic sensitivity was found to be specific to Mcm2 or Mcm4 overexpression, further pointing to the importance of the DDK-MCM ring interaction. ..