Genomes and Genes
Gene Symbol: MCM7
Description: mini-chromosome maintenance complex protein 7
Alias: CDC47, mini-chromosome maintenance complex protein 7
Species: Saccharomyces cerevisiae S288c
- Seki T, Diffley J. Stepwise assembly of initiation proteins at budding yeast replication origins in vitro. Proc Natl Acad Sci U S A. 2000;97:14115-20 pubmed..Extracts from cells arrested in mitosis also can support the binding of ORC but are unable to load either Cdc6p or MCM2-7 proteins. This system should be useful for studying the mechanism and regulation of pre-RC assembly. ..
- Labib K, Tercero J, Diffley J. Uninterrupted MCM2-7 function required for DNA replication fork progression. Science. 2000;288:1643-7 pubmed..Restricting MCM loading to the G(1) phase ensures that initiation and elongation occur just once per cell cycle. ..
- Kanter D, Bruck I, Kaplan D. Mcm subunits can assemble into two different active unwinding complexes. J Biol Chem. 2008;283:31172-82 pubmed publisher..We studied the mechanism of the Mcm4-Mcm6-Mcm7 complex, a useful model system because this complex has helicase activity in vitro...
- Bochman M, Schwacha A. Differences in the single-stranded DNA binding activities of MCM2-7 and MCM467: MCM2 and MCM5 define a slow ATP-dependent step. J Biol Chem. 2007;282:33795-804 pubmed..We propose that the DNA binding differences between MCM2-7 and MCM467 correspond to a conformational change at the MCM2/5 active site with putative regulatory significance. ..
- Bochman M, Schwacha A. The Mcm2-7 complex has in vitro helicase activity. Mol Cell. 2008;31:287-93 pubmed publisher..Our results show that purified Mcm2-7 acts as a helicase, provides functional evidence of a Mcm2/5 gate, and lays the foundation for future mechanistic studies of this critical factor. ..
- 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. ..
- Coster G, Frigola J, Beuron F, Morris E, Diffley J. Origin licensing requires ATP binding and hydrolysis by the MCM replicative helicase. Mol Cell. 2014;55:666-77 pubmed publisher..This work alters our view of how ATP is used by licensing factors to assemble pre-RCs. ..
- Loo S, Fox C, Rine J, Kobayashi R, Stillman B, Bell S. The origin recognition complex in silencing, cell cycle progression, and DNA replication. Mol Biol Cell. 1995;6:741-56 pubmed..The silencing defect caused by orc5-1 strengthened previous connections between ORC and silencing, and combined with the phenotypes caused by orc2 mutations, suggested that the complex itself functions in both processes. ..
- Hennessy K, Lee A, Chen E, Botstein D. A group of interacting yeast DNA replication genes. Genes Dev. 1991;5:958-69 pubmedMutations in the cell-division-cycle genes CDC46 and CDC47 were originally isolated as suppressors of mutations in two other cell-division-cycle genes (CDC45 and CDC54)...
- 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. ..
- 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. ..
- Biswas Fiss E, Khopde S, Biswas S. The Mcm467 complex of Saccharomyces cerevisiae is preferentially activated by autonomously replicating DNA sequences. Biochemistry. 2005;44:2916-25 pubmed..Our results also indicate that the yeast replication protein A stimulated the ATPase activity of the Mcm467 complex. ..
- Ma X, Stead B, Rezvanpour A, Davey M. The effects of oligomerization on Saccharomyces cerevisiae Mcm4/6/7 function. BMC Biochem. 2010;11:37 pubmed publisher..In keeping with this observation, Mcm4/6/7 binds DNA as a hexamer. The minimal functional unit of Mcm4/6/7 is a hexamer. One of the roles of ATP binding by Mcm4/6/7 may be to stabilize formation of hexamers. ..
- Zou L, Stillman B. Formation of a preinitiation complex by S-phase cyclin CDK-dependent loading of Cdc45p onto chromatin. Science. 1998;280:593-6 pubmed
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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
- 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. ..
- 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..Cdc6, Clb/Cdc28 kinases were necessary and sufficient for efficient net nuclear export of a fusion protein between Mcm7 and the green fluorescent protein (Mcm7-GFP), whereas inactivation of these kinases at the end of mitosis coincided ..
- 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. ..
- 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. ..
- 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..We characterize two mutations in CDC47 and CDC46 which arrest cells with unduplicated DNA as a result of single base substitutions...
- 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. ..
- Bochman M, Schwacha A. The Saccharomyces cerevisiae Mcm6/2 and Mcm5/3 ATPase active sites contribute to the function of the putative Mcm2-7 'gate'. Nucleic Acids Res. 2010;38:6078-88 pubmed publisher..This heterohexameric helicase contains six different and essential subunits (Mcm2 through Mcm7), with the corresponding dimer interfaces forming ATPase active sites from conserved motifs of adjacent subunits...
- Dalton S, Whitbread L. Cell cycle-regulated nuclear import and export of Cdc47, a protein essential for initiation of DNA replication in budding yeast. Proc Natl Acad Sci U S A. 1995;92:2514-8 pubmedThe CDC47 gene was isolated by complementation of a cdc47 temperature-sensitive mutant in Saccharomyces cerevisiae and was shown to encode a predicted polypeptide, Cdc47, of 845 aa...
- 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. ..
- 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. ..
- 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..the tethering of SCF(Dia2) to the replisome progression complex increases the efficiency of ubiquitylation of the Mcm7 subunit of CMG, both in vitro and in vivo...
- 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. ..
- Miyazawa Onami M, Araki H, Tanaka S. Pre-initiation complex assembly functions as a molecular switch that splits the Mcm2-7 double hexamer. EMBO Rep. 2017;18:1752-1761 pubmed publisher..In the pre-IC, the Mcm2-7 double hexamer is separated into single hexamers, as in the active helicase. Our data indicate that pre-IC assembly functions as an all-or-nothing molecular switch that splits the Mcm2-7 double hexamer. ..
- 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. ..
- 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 absence of ..
- Schepers A, Diffley J. Mutational analysis of conserved sequence motifs in the budding yeast Cdc6 protein. J Mol Biol. 2001;308:597-608 pubmed..Overexpression of this mutant protein is lethal. This phenotype is very similar to the phenotype previously described for a mutation in the Walker B motif, suggesting a common role for sensor I and the Walker B motif in Cdc6 function. ..
- Araki Y, Kawasaki Y, Sasanuma H, Tye B, Sugino A. Budding yeast mcm10/dna43 mutant requires a novel repair pathway for viability. Genes Cells. 2003;8:465-80 pubmed..Mcm10p functionally interacts with components of the pre-replicative complex (Mcm2-Mcm7 complex and origin recognition complex) as well as the pre-initiation complex component (Cdc45p) suggesting that it ..
- 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. ..
- 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. ..
- Su N, Flick K, Kaiser P. The F-box protein Met30 is required for multiple steps in the budding yeast cell cycle. Mol Cell Biol. 2005;25:3875-85 pubmed..chromatin immunoprecipitation experiments revealed significantly lower levels of the replication factors Mcm4, Mcm7, and Cdc45 at replication origins in met30 mutants than in wild-type cells...
- 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...
- Fitch M, Donato J, Tye B. Mcm7, a subunit of the presumptive MCM helicase, modulates its own expression in conjunction with Mcm1. J Biol Chem. 2003;278:25408-16 pubmedThe Saccharomyces cerevisiae Mcm7 protein is a subunit of the presumed heteromeric MCM helicase that melts origin DNA and unwinds replication forks...
- 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. ..
- 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. ..
- Hoang M, Leon R, Pessoa Brandao L, Hunt S, Raghuraman M, Fangman W, et al. Structural changes in Mcm5 protein bypass Cdc7-Dbf4 function and reduce replication origin efficiency in Saccharomyces cerevisiae. Mol Cell Biol. 2007;27:7594-602 pubmed..Because similar mutations in mcm2 and mcm4 cannot bypass DDK, Mcm5 protein may be a unique Mcm protein that is the final target of DDK regulation. ..
- 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. ..
- 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. ..
- Homesley L, Lei M, Kawasaki Y, Sawyer S, Christensen T, Tye B. Mcm10 and the MCM2-7 complex interact to initiate DNA synthesis and to release replication factors from origins. Genes Dev. 2000;14:913-26 pubmed..Surprisingly, a double mutant containing both the mcm10-1 and mcm7-1 (cdc47-1) alleles restores interaction between Mcm10 and Mcm7 and corrects all of the defects exhibited by each of the ..
- Ticau S, Friedman L, Ivica N, Gelles J, Bell S. Single-molecule studies of origin licensing reveal mechanisms ensuring bidirectional helicase loading. Cell. 2015;161:513-525 pubmed publisher..Our findings reveal the complex protein dynamics that coordinate helicase loading and indicate that distinct mechanisms load the oppositely oriented helicases that are central to bidirectional replication initiation. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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..Possible roles for ubiquitinated Mcm3p in the assembly of the MCM complex at replication origins are discussed. ..
- 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. ..
- Tanaka T, Knapp D, Nasmyth K. Loading of an Mcm protein onto DNA replication origins is regulated by Cdc6p and CDKs. Cell. 1997;90:649-60 pubmed..Our data suggest that the loading of Mcm proteins onto origins is regulated by two mechanisms: first, by Cdc6p occupancy, and second, by S- and M-CDKs, whose activity during S, G2, and M phases prevents Mcm loading. ..