Affinage

MCM7

DNA replication licensing factor MCM7 · UniProt P33993

Round 2 corrected
Length
719 aa
Mass
81.3 kDa
Annotated
2026-04-28
130 papers in source corpus 31 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MCM7 is an essential subunit of the MCM2-7 heterohexameric complex that functions as the core replicative DNA helicase in eukaryotes, central to origin licensing, replication fork progression, checkpoint signaling, and epigenetic maintenance during S phase. The MCM4-MCM6-MCM7 subcomplex possesses intrinsic 3′→5′ DNA helicase activity requiring MCM7 ATPase motifs, and the full MCM2-7 complex is loaded onto origin DNA as a head-to-head double hexamer by ORC–Cdc6–Cdt1, with sequential ATP-hydrolysis-driven ring closure; CDK phosphorylation of ORC prevents re-licensing while DDK phosphorylation across the double-hexamer interface activates the helicase for CMG formation (PMID:9305914, PMID:19896182, PMID:28191892, PMID:35614055, PMID:37428921). MCM7 directly interacts with Rb (whose inhibitory binding is relieved by cyclin D1/CDK4), cyclin A (required for S-phase entry), hRad17 (coupling the replisome to the ATR–Chk1 checkpoint), and MCM-BP (which unloads MCM2-7 at replication termination), and the MCM2-7 complex is O-GlcNAcylated on chromatin to stabilize subunit interactions (PMID:9566894, PMID:12519773, PMID:21078875, PMID:15538388, PMID:21196493, PMID:30069701). Biallelic pathogenic variants in MCM7 cause Meier-Gorlin syndrome with associated lipodystrophy and adrenal insufficiency (PMID:33654309).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1997 High

    Identification of the MCM4/6/7 subcomplex as a 3′→5′ DNA helicase established that MCM proteins are the long-sought replicative helicase candidates in eukaryotes.

    Evidence Biochemical purification from HeLa cells with ATPase and helicase assays, immunodepletion validation

    PMID:9305914

    Open questions at the time
    • Full hexameric MCM2-7 helicase activity not yet demonstrated
    • Processivity and in vivo relevance not addressed
  2. 1998 High

    Discovery that Rb directly binds MCM7 and inhibits DNA replication in an MCM7-dependent manner revealed the first direct mechanistic link between a tumor suppressor and the replication licensing machinery.

    Evidence Yeast two-hybrid, co-IP from human cells, Xenopus in vitro replication assay with Rb N-terminal domain

    PMID:9566894

    Open questions at the time
    • Phosphorylation-dependent regulation of Rb–MCM7 not yet tested
    • In vivo relevance in mammalian cells not demonstrated
  3. 1999 High

    Systematic mutagenesis of ATPase motifs across MCM4/6/7 subunits demonstrated that MCM7 ATPase activity is essential for both ATPase and helicase function of the complex, while individual subunits contribute distinct biochemical properties.

    Evidence Site-directed mutagenesis of Walker A/B motifs, insect cell expression, in vitro ATPase and helicase assays

    PMID:10567526 PMID:12207017

    Open questions at the time
    • Contributions of MCM2, MCM3, and MCM5 ATPase sites not yet analyzed
    • No structural context for inter-subunit ATPase coupling
  4. 2003 High

    Cyclin D1/CDK4 was shown to relieve Rb-mediated inhibition of MCM7 by catalyzing dissociation of the Rb–MCM7 complex on chromatin, connecting cell-cycle kinase signaling directly to licensing factor regulation.

    Evidence Co-IP, chromatin fractionation, in vitro Rb–MCM7 dissociation assay with purified kinases

    PMID:12519773

    Open questions at the time
    • Phosphorylation sites on Rb or MCM7 mediating dissociation not mapped
    • Redundancy with CDK2 pathways not resolved
  5. 2004 High

    MCM7 was found to physically interact with hRad17 and to be required for ATR focus formation and Chk1 phosphorylation after replication stress, establishing MCM7 as a critical node coupling the replisome to S-phase checkpoint activation.

    Evidence Co-IP of MCM7–hRad17, siRNA depletion with UV/aphidicolin challenge, Chk1 phosphorylation and ATR focus readouts

    PMID:15538388

    Open questions at the time
    • Whether MCM7–Rad17 interaction is direct or mediated through other replisome components
    • Structural basis of checkpoint coupling unknown
  6. 2007 High

    Demonstration that excess chromatin-loaded MCM2-7 licenses dormant origins that fire upon replication stress explained the 'MCM paradox' — why cells load far more MCM complexes than are needed for normal replication.

    Evidence RNAi reduction of chromatin MCM2-7, DNA fiber analysis, replication inhibitor challenge in human cells

    PMID:18079179

    Open questions at the time
    • Mechanism selecting which dormant origins fire remains unclear
    • Regulation of excess MCM loading stoichiometry not defined
  7. 2009 High

    Complete in vitro reconstitution of MCM2-7 double-hexamer loading by ORC–Cdc6–Cdt1 on DNA, visualized by EM, established the architecture and cooperativity of origin licensing.

    Evidence Purified yeast protein reconstitution, electron microscopy, biochemical sliding assay

    PMID:19896182 PMID:19910535

    Open questions at the time
    • Mechanism of second hexamer recruitment not resolved
    • How origin DNA sequence specificity is enforced during loading
  8. 2010 High

    Two key regulatory interactions were defined: MCM-BP specifically binds MCM7 and unloads MCM2-7 from chromatin at replication termination, while cyclin A–MCM7 interaction is essential for S-phase entry, linking licensing to cell-cycle progression.

    Evidence Immunodepletion and recombinant MCM-BP addition in Xenopus extracts; reciprocal mutant suppression of cyclin A–MCM7 binding with FACS

    PMID:21078875 PMID:21196493

    Open questions at the time
    • How MCM-BP selectively targets MCM7 within MCM2-7 structurally
    • Whether cyclin A–MCM7 interaction involves CDK2 kinase activity or is purely structural
  9. 2010 High

    The intronic miR-106b~25 cluster cooperates with host gene MCM7 in oncogenic transformation, demonstrating that MCM7 locus amplification delivers a dual oncogenic signal.

    Evidence Transgenic mouse model developing prostatic intraepithelial neoplasia, in vitro transformation assays

    PMID:20388916

    Open questions at the time
    • Relative contribution of MCM7 protein vs. miRNA cluster to tumorigenesis not fully separated
    • Relevance to human cancers beyond prostate not directly tested
  10. 2014 High

    Systematic ATPase mutagenesis across all six MCM2-7 subunits separated loading-specific from activation-specific ATPase functions, revealing that individual active sites play non-redundant roles during distinct steps of helicase assembly.

    Evidence Walker A/B mutations in each subunit with loading, Cdt1 release, GINS recruitment, and unwinding assays

    PMID:25087876

    Open questions at the time
    • Structural basis for allosteric coordination among the six ATPase sites unknown at this point
    • How DDK and CDK integrate with subunit-specific ATPase requirements
  11. 2017 High

    Near-atomic cryo-EM structures of the OCCM loading intermediate and the double hexamer on DNA, together with single-molecule FRET tracking of ring closure, provided a mechanistic model for stepwise, ATP-hydrolysis-coupled hexamer loading and revealed how DNA threads through the central channel with subunit-specific contacts.

    Evidence Cryo-EM at 3.9 Å (OCCM) and double-hexamer structures; single-molecule FRET/colocalization spectroscopy

    PMID:28191892 PMID:28191893 PMID:29078375

    Open questions at the time
    • Transition from double hexamer to two active CMG complexes not structurally resolved
    • Strand extrusion mechanism at the Mcm2–Mcm5 gate remains a model
  12. 2018 Medium

    O-GlcNAcylation of chromatin-bound MCM7 (and MCM2/3/6) by OGT was shown to stabilize MCM subunit interactions on chromatin, adding a metabolic regulatory layer to replication licensing.

    Evidence Co-IP of OGT with MCM2-7, OGT knockdown, chromatin fractionation, O-GlcNAc detection

    PMID:30069701

    Open questions at the time
    • Specific O-GlcNAcylation sites on MCM7 not mapped
    • Functional consequence for replication timing or origin firing not tested
  13. 2019 Medium

    MCM7 was found to have a replication-independent role in ciliogenesis: MCM2-7 occupies cilia gene promoters in non-cycling cells, and MCM7 depletion causes cilia shortening and ciliopathy phenotypes in zebrafish.

    Evidence MCM7 siRNA in quiescent human fibroblasts, zebrafish morpholino, MCM2 ChIP at TSS of cilia genes, cilia length measurements

    PMID:30329080

    Open questions at the time
    • Direct MCM7 ChIP at cilia gene promoters not shown (MCM2 ChIP used)
    • Transcriptional mechanism in post-mitotic cells not defined
  14. 2021 Medium

    Biallelic MCM7 variants were identified as causative for Meier-Gorlin syndrome with lipodystrophy and adrenal insufficiency, placing MCM7 among origin-licensing factors whose hypomorphic loss causes primordial dwarfism.

    Evidence Exome/genome sequencing of affected families, functional studies of MCM complex formation and S-phase defects in patient cells

    PMID:33654309

    Open questions at the time
    • Genotype-phenotype correlation across different MCM7 variants not established
    • Tissue-specific sensitivity to reduced MCM7 function unexplained
  15. 2022 High

    Cryo-EM structures of DDK on the MCM2-7 double hexamer revealed the trans-hexamer phosphorylation mechanism by which DDK bridges across the double-hexamer interface to phosphorylate MCM4, MCM2, and MCM6, directly explaining how activation signals are transmitted.

    Evidence Cryo-EM structure determination with biochemical phosphorylation validation

    PMID:35614055

    Open questions at the time
    • How DDK phosphorylation is coordinated with Cdc45/GINS recruitment in vivo
    • Whether DDK phosphorylates MCM7 directly or only indirectly affects it
  16. 2023 High

    CDK phosphorylation of ORC was shown to block MO complex formation and prevent stable first-ring closure, providing the molecular mechanism for CDK-mediated re-replication prevention at the level of initial Mcm2-7 recruitment.

    Evidence Single-molecule real-time monitoring of licensing with phospho-ORC mutants (Orc2, Orc6)

    PMID:37428921

    Open questions at the time
    • Whether this mechanism operates identically at all origins or is origin-class dependent
    • Integration with geminin and Cdt1 degradation pathways in metazoans
  17. 2023 Medium

    FACT subunit Spt16 was shown to interact with MCM2-7 and facilitate parental histone recycling specifically to lagging strands during replication, linking the MCM helicase to epigenetic inheritance.

    Evidence Spt16-N deletion mutants, FACT–MCM co-IP, strand-specific parental histone recycling assays

    PMID:37850662

    Open questions at the time
    • Direct contact surface between Spt16 and MCM7 specifically not mapped
    • Whether MCM7 has a unique role vs. other MCM subunits in histone transfer

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of the double-hexamer-to-two-CMG transition during origin firing, the specific O-GlcNAcylation and ubiquitylation sites on MCM7 and their functional consequences, the mechanism of MCM7's replication-independent transcriptional role in ciliogenesis, and genotype-phenotype relationships for MCM7 variants in Meier-Gorlin syndrome.
  • Structural intermediates between double hexamer and active bidirectional CMG pair not captured
  • MCM7-specific post-translational modification map incomplete
  • Replication-independent transcriptional mechanism in quiescent cells mechanistically undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 5 GO:0140097 catalytic activity, acting on DNA 4 GO:0003677 DNA binding 3
Localization
GO:0005694 chromosome 5 GO:0005634 nucleus 3
Pathway
R-HSA-69306 DNA Replication 8 R-HSA-1640170 Cell Cycle 5 R-HSA-73894 DNA Repair 2
Partners
ARCCNA2MCMBPOGTPLK1PRMT5RAD17RB1
Complex memberships
CMG (Cdc45-MCM2-7-GINS) holohelicaseMCM2-7 hexamerMCM4-MCM6-MCM7 subcomplexOCCM (ORC-Cdc6-Cdt1-Mcm2-7)

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 The MCM4-MCM6-MCM7 subcomplex purified from HeLa cells possesses intrinsic DNA helicase activity (3'→5' directionality) dependent on hydrolyzable ATP, identifying the MCM complex as a replicative helicase candidate. Biochemical purification, co-purification of ATPase and helicase activities, immunodepletion with anti-MCM4 antibody The Journal of biological chemistry High 9305914
1998 Retinoblastoma protein (Rb) and its relatives p107 and p130 physically interact with MCM7 both in vitro and in immunoprecipitates from human cells; the Rb amino-terminus inhibits DNA replication in a Xenopus system in an MCM7-dependent manner, providing the first evidence that Rb directly regulates DNA replication by targeting a licensing factor. Yeast two-hybrid screen, in vitro binding assay, co-immunoprecipitation from human cells, Xenopus in vitro DNA replication assay with Rb N-terminal domain Molecular and cellular biology High 9566894
1999 The intrinsic DNA helicase activity of the Mcm4/6/7 complex requires the ATP-binding activity of Mcm6; Mcm7 ATPase motifs are essential for both ATPase and helicase activities of the complex, while Mcm4 contributes to single-stranded DNA binding and subunit interaction. The two activities (helicase and ssDNA binding) can be separated. Mutagenesis of conserved ATPase motifs in Mcm4 and Mcm6, expression in insect cells, in vitro ATPase and helicase assays Molecular and cellular biology High 10567526
2002 Conserved ATPase motifs of Mcm7 are essential for ATPase and DNA helicase activities of the mouse Mcm4/6/7 complex; uncomplexed Mcm7 has no intrinsic activity, indicating its contribution depends on interaction with partner subunits. The Mcm4 zinc-finger domain regulates subunit interactions and negatively regulates helicase activity when mutated. ATPase motif mutagenesis of Mcm7 and Mcm4, expression/purification of mutant Mcm4/6/7 complexes, in vitro ATPase and helicase assays The Journal of biological chemistry High 12207017
2003 Cyclin D1/CDK4 associates with chromatin-bound MCM7 and MCM3; active cyclin D1/CDK4 (but not cyclin E/CDK2) catalyzes dissociation of the RB·MCM7 inhibitory complex and promotes removal of RB from chromatin, suggesting CDK4 relieves Rb-mediated inhibition of MCM7 licensing activity to prepare origins for replication. Yeast two-hybrid, co-immunoprecipitation, kinase assays, chromatin fractionation, in vitro RB·MCM7 dissociation assay The Journal of biological chemistry High 12519773
2003 Saccharomyces cerevisiae Mcm7 acts as a transcriptional co-factor of Mcm1, stimulating Mcm1 binding to the early cell cycle box (ECB) in the MCM7, CDC6, and MCM5 promoters; Mcm7 is recruited to these promoters during late M phase to modulate M/G1-specific expression of replication genes, revealing a novel autoregulatory loop. Genetic analysis of mcm7-1 and mcm1-1 mutants, in vitro Mcm1 binding assays, chromatin immunoprecipitation The Journal of biological chemistry Medium 12738768
2004 Human MCM7 physically interacts with hRad17; depletion of hMCM7 by siRNA suppresses UV- and aphidicolin-induced Chk1 phosphorylation, abolishes S-phase checkpoint activation, and impairs ATR nuclear focus formation after UV irradiation, demonstrating that MCM7 is required for transmission of replication stress signals to the checkpoint machinery. siRNA knockdown of hMCM7, co-immunoprecipitation with hRad17, Chk1 phosphorylation assay, ATR focus formation by immunofluorescence, S-phase checkpoint assay The EMBO journal High 15538388
2005 Plk1 polo-box domain interacts with Mcm2 and Mcm7; endogenous Plk1 co-immunoprecipitates with basal and DNA-damage-induced forms of Mcm7, with the strongest interaction detected in the soluble chromatin fraction, suggesting a functional link between Plk1 and MCM complexes in coordinating DNA replication and mitotic events. Polo-box domain pull-down screen, co-immunoprecipitation, immunoblot, chromatin fractionation The Journal of biological chemistry Medium 15654075
2007 Dormant replication origins licensed by excess chromatin-bound MCM2-7 are activated within active replicon clusters upon replication fork inhibition; RNAi-mediated reduction of chromatin-bound MCM2-7 in human cells suppresses dormant origin firing during replicative stress and dramatically reduces DNA synthesis rates and cell viability, establishing a physiologically important role for excess MCM loading. RNAi knockdown of MCM2-7 in human cells, DNA fiber analysis, BrdU incorporation, replication inhibitor challenge (aphidicolin, HU), cell viability assays Genes & development High 18079179
2008 MCM7 interacts with the androgen receptor (AR) through defined binding motifs (MCM7 aa 221–248; AR aa 426–475); high-dose androgen reduces MCM7 binding to genomic DNA and DNA synthesis while low-dose androgen increases licensing activity; MCM7/AR interaction down-regulates MCM7 expression and AR transcriptional activity depends on MCM7. Co-immunoprecipitation in vitro and in vivo, deletion mutagenesis mapping of binding domains, chromatin-bound MCM7 assay, BrdU incorporation, siRNA knockdown of MCM7 The American journal of pathology Medium 18988800
2009 Purified budding yeast Mcm2-7 complexes are loaded cooperatively by ORC, Cdc6, and Cdt1 onto DNA as stable head-to-head double hexamers; the DNA runs through the central channel, and once loaded the double hexamer can slide passively along double-stranded DNA. Reconstitution of pre-RC with purified yeast proteins, electron microscopy, biochemical sliding assay Cell High 19896182 19910535
2010 MCM-BP (MCM-binding protein) forms a stable complex specifically with MCM7 (not with the full MCM2-7 hexamer) and accumulates in nuclei during late S phase; MCM-BP immunodepletion in Xenopus egg extracts blocks replication-dependent MCM2-7 dissociation from chromatin without affecting pre-RC formation; excess MCM-BP promotes disassembly of the MCM2-7 complex and releases MCM2-7 from late-S-phase chromatin, establishing MCM-BP as an MCM2-7 unloader. Co-immunoprecipitation, Xenopus egg extract immunodepletion, recombinant MCM-BP addition to chromatin, siRNA in human cells Genes & development High 21196493
2010 The intronic miR-106b~25 cluster cooperates with its host gene MCM7 in cellular transformation both in vitro and in vivo; concomitant overexpression of MCM7 and the miRNA cluster triggers prostatic intraepithelial neoplasia in transgenic mice, demonstrating that the MCM7 locus delivers dual oncogenic insults when amplified. Transgenic mouse model, in vitro transformation assays, overexpression of MCM7 with/without miRNA cluster Science signaling High 20388916
2010 Cyclin A promotes S-phase entry through direct interaction with replication licensing factor Mcm7; a cyclin A mutant (CycA-C1) that cannot bind Mcm7 fails to promote S-phase entry, and an Mcm7 mutant (Mcm7-3) that associates with CycA-C1 suppresses this S-phase defect, demonstrating that the cyclin A–Mcm7 interaction is essential for S-phase entry. Mutant cyclin A design, yeast two-hybrid and co-immunoprecipitation (chromatin fraction), RNAi suppression, cell cycle analysis by FACS Molecular and cellular biology High 21078875
2013 CDK2/cyclin A phosphorylation of MCM4 within MCM2-7 inhibits the DNA-binding ability of the MCM2-7 complex as measured by gel-shift analysis; mutation of six Ser/Thr residues in the MCM4 N-terminal region renders the complex insensitive to CDK-mediated inhibition, suggesting CDK-phosphorylation of MCM4 directly prevents MCM2-7 chromatin re-loading to block re-replication. In vitro phosphorylation with purified CDK complexes, gel-shift (EMSA) DNA-binding assay, MCM4 alanine substitution mutants Journal of biochemistry High 23864661
2014 Individual Mcm2-7 ATPase active sites perform distinct functions during helicase loading and activation: ATP binding/hydrolysis by specific subunits is required for initial Mcm2-7 recruitment or Cdt1 release during loading; a subset of ATPase mutants complete loading but are defective in maintaining DNA association, GINS recruitment, or DNA unwinding during activation. ATPase-motif mutagenesis of each Mcm2-7 subunit, helicase loading assays, Cdt1 release assay, GINS recruitment assay, DNA unwinding assay Molecular cell High 25087876
2017 Cryo-EM structure of the Saccharomyces cerevisiae OCCM (ORC-Cdc6-Cdt1-Mcm2-7) complex on DNA at 3.9 Å reveals that flexible Mcm2-7 winged-helix domains engage ORC-Cdc6; Cdt1 embraces Mcm2, Mcm4, and Mcm6 (nearly half the hexamer) and its C-terminal domain contacts Mcm6 WHD–Orc4 WHD; origin DNA passes through both rings; the Mcm2-7 C-tier ring is topologically closed by an Mcm5 loop embracing Mcm2, while the N-tier Mcm2-Mcm5 interface remains open. Cryo-EM structure determination at 3.9 Å with functional validation Nature structural & molecular biology High 28191893
2017 Single-molecule FRET and colocalization spectroscopy reveal that the two Mcm2-7 rings are open during initial DNA association and close sequentially, concomitant with Cdt1 release; ATP hydrolysis by Mcm2-7 drives ring closure; failure to load the first Mcm2-7 prevents recruitment of the second Mcm2-7. Single-molecule FRET, colocalization single-molecule spectroscopy, ATP hydrolysis mutants Nature structural & molecular biology High 28191892
2017 Cryo-EM structure of the Mcm2-7 double hexamer on dsDNA shows DNA is zigzagged inside the central channel; PS1 loops of Mcm3, 4, 6, and 7 (but not 2 and 5) engage the lagging strand with ~1 base per subunit step size; staggered hexamer coupling positions each DNA strand at one Mcm2-Mcm5 gate, suggesting lagging-strand extrusion initiates in the middle of the double hexamer. Cryo-EM structure of Mcm2-7 double hexamer on dsDNA, loop-DNA contact analysis Proceedings of the National Academy of Sciences of the United States of America High 29078375
2018 Polyubiquitylation of MCM7 is involved in terminating MCM function at the end of DNA replication; CDK and DDK kinases as well as MCM10 are required to activate the CMG helicase from the loaded Mcm2-7 double hexamer; CDK phosphorylation primarily prevents re-initiation by inhibiting helicase loading. Review synthesizing structural and functional analyses of CMG; specific data on MCM7 polyubiquitylation from referenced biochemical studies Genes & genetic systems Medium 30369561
2018 O-GlcNAc transferase (OGT) associates with the MCM2-7 complex and O-GlcNAcylates MCM2, MCM3, MCM6, and MCM7 preferentially in the chromatin-bound fraction; OGT silencing decreases chromatin binding of MCM2, MCM6, and MCM7 and destabilizes MCM2/6 and MCM4/7 interactions in chromatin, implicating O-GlcNAcylation in MCM2-7 complex stability on chromatin. Co-immunoprecipitation, OGT knockdown, chromatin fractionation, O-GlcNAc detection in synchronized cells Cellular and molecular life sciences Medium 30069701
2019 A conserved Mcm4 motif is required for stable Mcm2-7 double-hexamer formation; mutations in this motif allow initial hexamer-hexamer contact but produce an unstable complex; double-hexamer formation is required for extensive origin DNA unwinding but not for initial DNA melting or recruitment of helicase-activation proteins (Cdc45, GINS, Mcm10). Single-molecule imaging, kinetic analysis of mutant Mcm2-7, DNA unwinding assays, helicase-activator recruitment assays eLife High 31385807
2019 Arsenic trioxide (ATO) suppresses MCM7 transcription by targeting the SRF/MCM7 complex, which functions as a transcriptional regulator of MCM7 expression; MCM7 knockdown recapitulates ATO's inhibitory effects on cancer stem cell traits and metastasis in HCC mouse models, while MCM7 overexpression rescues these effects. Co-immunoprecipitation of SRF-MCM7 complex, MCM7 knockdown/overexpression in mouse tumor models, promoter assays Cell death & disease Medium 31186405
2019 MCM2 (in complex with MCM7) binds transcription start sites of cilia-inhibiting genes in non-cycling human fibroblasts; MCM7 depletion causes cilia shortening and centriole overduplication in non-cycling cells and ciliopathy phenotypes in zebrafish, revealing a replication-independent role for MCM7 in ciliogenesis. MCM7 siRNA knockdown in non-cycling fibroblasts, zebrafish morpholino depletion, chromatin immunoprecipitation (MCM2), cilia length measurement, centriole imaging Nucleic acids research Medium 30329080
2021 PRMT5 physically interacts with MCM7 through direct binding to MCM7 residues 1–248 as shown by co-immunoprecipitation; both proteins promote colorectal cancer cell proliferation, migration, and invasion in vitro and in vivo. Co-immunoprecipitation with domain-mapping deletion mutants, shRNA knockdown, xenograft models Journal of cellular and molecular medicine Medium 33675123
2021 Biallelic pathogenic variants in MCM7 cause Meier-Gorlin syndrome or a multi-system disorder with lipodystrophy and adrenal insufficiency; functional studies confirm that MCM7 variants are deleterious and impair MCM complex formation, affecting S-phase progression efficiency. Exome and genome sequencing, functional studies of MCM complex formation and S-phase progression in patient-derived cells European journal of human genetics Medium 33654309
2022 Cryo-EM structure of the Dbf4-Cdc7 (DDK) kinase on the MCM2-7 double hexamer reveals that the Dbf4 HBRCT domain anchors DDK to Mcm2; DDK bridges across the double-hexamer interface to phosphorylate Mcm4 on the opposite hexamer; rotation of DDK along this anchoring point also enables phosphorylation of Mcm2 and Mcm6. Cryo-EM structure determination, biochemical phosphorylation assays with defined substrates Nature communications High 35614055
2022 Cryo-EM structure of endogenous human MCM2-7 hexamer at 4.4 Å reveals an open-ring conformation with a gap between Mcm2 and Mcm5; human MCM2-7 can self-associate into a loose double hexamer, potentially implying a novel chromatin-loading mechanism. Cryo-EM structure of endogenous human MCM2-7 iScience Medium 36117988
2023 The N-terminus of Spt16 (FACT subunit) interacts with the MCM2-7 replicative helicase and facilitates formation of a ternary complex among FACT, histone H3/H4, and the Mcm2 histone-binding domain; this interaction is critical for recycling and transfer of parental histones to lagging strands during replication, with Spt16-N deletion specifically impairing lagging-strand parental histone recycling. Protein interaction assays, Spt16-N deletion mutants, parental histone recycling assays on leading/lagging strands, FACT-MCM co-immunoprecipitation Nucleic acids research Medium 37850662
2023 CDK phosphorylation of ORC prevents second Mcm2-7 recruitment; ORC phosphorylation causes rapid simultaneous release of the first Mcm2-7 and Cdt1, and prevents stable Mcm2-7 ring encirclement of origin DNA; MO (Mcm2-7–ORC) complex formation, which requires the closed-ring form of Mcm2-7, is fully inhibited by ORC phosphorylation and is required to complete stable first-ring closure. Single-molecule assays for multiple licensing events, phospho-ORC mutants (Orc2, Orc6), real-time monitoring of Mcm2-7 ring closing Proceedings of the National Academy of Sciences of the United States of America High 37428921

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science (New York, N.Y.) 2197 12791985
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2001 DNA replication in eukaryotic cells. Annual review of biochemistry 1405 12045100
2016 ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. Cell 1233 26777405
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2005 Nucleolar proteome dynamics. Nature 934 15635413
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2004 A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nature cell biology 841 14743216
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2011 Global landscape of HIV-human protein complexes. Nature 593 22190034
2009 Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing. Cell 548 19896182
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2007 Dormant origins licensed by excess Mcm2-7 are required for human cells to survive replicative stress. Genes & development 474 18079179
1997 A DNA helicase activity is associated with an MCM4, -6, and -7 protein complex. The Journal of biological chemistry 461 9305914
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 of the United States of America 438 19910535
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2009 Purification of proteins associated with specific genomic Loci. Cell 436 19135898
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2016 Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. Cell 423 26871637
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2004 Self-assembling protein microarrays. Science (New York, N.Y.) 409 15232106
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2015 Proteome-wide profiling of protein assemblies by cross-linking mass spectrometry. Nature methods 370 26414014
2010 Identification of the miR-106b~25 microRNA cluster as a proto-oncogenic PTEN-targeting intron that cooperates with its host gene MCM7 in transformation. Science signaling 361 20388916
1997 Mcm2 is a target of regulation by Cdc7-Dbf4 during the initiation of DNA synthesis. Genes & development 259 9407029
1991 Mcm2 and Mcm3, two proteins important for ARS activity, are related in structure and function. Genes & development 184 2044961
1995 Gene trap tagging of PROLIFERA, an essential MCM2-3-5-like gene in Arabidopsis. Science (New York, N.Y.) 181 7754372
1999 Biochemical analysis of the intrinsic Mcm4-Mcm6-mcm7 DNA helicase activity. Molecular and cellular biology 180 10567526
1997 A novel Mcm1-dependent element in the SWI4, CLN3, CDC6, and CDC47 promoters activates M/G1-specific transcription. Genes & development 168 9171372
1998 Negative regulation of DNA replication by the retinoblastoma protein is mediated by its association with MCM7. Molecular and cellular biology 167 9566894
2001 Replication factors MCM2 and ORC1 interact with the histone acetyltransferase HBO1. The Journal of biological chemistry 162 11278932
2017 Structural basis of Mcm2-7 replicative helicase loading by ORC-Cdc6 and Cdt1. Nature structural & molecular biology 139 28191893
2005 Pumps, paradoxes and ploughshares: mechanism of the MCM2-7 DNA helicase. Trends in biochemical sciences 127 16002295
2000 The essential Mcm7 protein PROLIFERA is localized to the nucleus of dividing cells during the G(1) phase and is required maternally for early Arabidopsis development. Development (Cambridge, England) 118 10751170
2014 Histone deacetylase inhibitor SAHA epigenetically regulates miR-17-92 cluster and MCM7 to upregulate MICA expression in hepatoma. British journal of cancer 102 25393367
2021 Pharmacoinformatics and molecular dynamics simulation-based phytochemical screening of neem plant (Azadiractha indica) against human cancer by targeting MCM7 protein. Briefings in bioinformatics 100 33834183
2006 Deregulated minichromosomal maintenance protein MCM7 contributes to oncogene driven tumorigenesis. Oncogene 98 16518415
2004 Interaction between human MCM7 and Rad17 proteins is required for replication checkpoint signaling. The EMBO journal 92 15538388
2014 Multiple functions for Mcm2-7 ATPase motifs during replication initiation. Molecular cell 90 25087876
2017 Cryo-EM structure of Mcm2-7 double hexamer on DNA suggests a lagging-strand DNA extrusion model. Proceedings of the National Academy of Sciences of the United States of America 88 29078375
2014 Structural and mechanistic insights into Mcm2-7 double-hexamer assembly and function. Genes & development 86 25319829
2010 DNA damage response and tumorigenesis in Mcm2-deficient mice. Oncogene 82 20440269
2004 DNA replication regulation protein Mcm7 as a marker of proliferation in prostate cancer. Journal of clinical pathology 81 15452160
2000 An MCM2-related gene is expressed in proliferating cells of intact and regenerating planarians. Developmental dynamics : an official publication of the American Association of Anatomists 78 10906779
2002 Minichromosome maintenance protein MCM7 is a direct target of the MYCN transcription factor in neuroblastoma. Cancer research 76 11861392
2018 Regulation of MCM2-7 function. Genes & genetic systems 75 30369561
2003 The cyclin D1-dependent kinase associates with the pre-replication complex and modulates RB.MCM7 binding. The Journal of biological chemistry 75 12519773
2017 Mechanism and timing of Mcm2-7 ring closure during DNA replication origin licensing. Nature structural & molecular biology 69 28191892
2015 Dynamic loading and redistribution of the Mcm2-7 helicase complex through the cell cycle. The EMBO journal 67 25555795
2002 Roles of Mcm7 and Mcm4 subunits in the DNA helicase activity of the mouse Mcm4/6/7 complex. The Journal of biological chemistry 64 12207017
2017 MCM2: An alternative to Ki-67 for measuring breast cancer cell proliferation. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 61 28084344
2019 Arsenic trioxide inhibits liver cancer stem cells and metastasis by targeting SRF/MCM7 complex. Cell death & disease 59 31186405
2008 Expression of Mcm-2, Ki-67 and geminin in benign and malignant salivary gland tumours. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 58 18248354
2018 Role of MCM2-7 protein phosphorylation in human cancer cells. Cell & bioscience 57 30062004
2009 Dbf4-Cdc7 phosphorylation of Mcm2 is required for cell growth. The Journal of biological chemistry 55 19692334
2016 MCM7 and its hosted miR-25, 93 and 106b cluster elicit YAP/TAZ oncogenic activity in lung cancer. Carcinogenesis 54 27797825
2010 Clinicopathological features and immunohistochemical expression of p53, Ki-67, Mcm-2 and Mcm-5 in proliferative verrucous leukoplakia. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 53 20412398
2010 MCM-BP regulates unloading of the MCM2-7 helicase in late S phase. Genes & development 53 21196493
2005 Replicative MCM7 protein as a proliferation marker in endometrial carcinoma: a tissue microarray and clinicopathological analysis. Histopathology 51 15720416
1998 Cloning and characterization of human MCM7 promoter. Gene 50 9714754
2001 Biochemical activities associated with mouse Mcm2 protein. The Journal of biological chemistry 49 11568184
2022 MCM2 in human cancer: functions, mechanisms, and clinical significance. Molecular medicine (Cambridge, Mass.) 47 36303105
2005 Interaction of chromatin-associated Plk1 and Mcm7. The Journal of biological chemistry 45 15654075
2017 Simvastatin suppresses the DNA replication licensing factor MCM7 and inhibits the growth of tamoxifen-resistant breast cancer cells. Scientific reports 44 28150753
2009 Dynamic localization of the DNA replication proteins MCM5 and MCM7 in plants. Plant physiology 44 19357199
2013 Interaction between human Ctf4 and the Cdc45/Mcm2-7/GINS (CMG) replicative helicase. Proceedings of the National Academy of Sciences of the United States of America 43 24255107
2003 Mcm7, a subunit of the presumptive MCM helicase, modulates its own expression in conjunction with Mcm1. The Journal of biological chemistry 43 12738768
2012 Post-transcriptional homeostasis and regulation of MCM2-7 in mammalian cells. Nucleic acids research 42 22362746
2001 Characterization of Schizosaccharomyces pombe mcm7(+) and cdc23(+) (MCM10) and interactions with replication checkpoints. Genetics 41 11606526
2012 The eukaryotic Mcm2-7 replicative helicase. Sub-cellular biochemistry 39 22918583
2022 Oxidative stress-induced circKIF18A downregulation impairs MCM7-mediated anti-senescence in intervertebral disc degeneration. Experimental & molecular medicine 38 35332256
2014 Switch on the engine: how the eukaryotic replicative helicase MCM2-7 becomes activated. Chromosoma 38 25308420
2010 Cyclin A promotes S-phase entry via interaction with the replication licensing factor Mcm7. Molecular and cellular biology 38 21078875
2022 MCM2 promotes the stemness and sorafenib resistance of hepatocellular carcinoma cells via hippo signaling. Cell death discovery 37 36243809
2022 Bioinformatics approaches identified dasatinib and bortezomib inhibit the activity of MCM7 protein as a potential treatment against human cancer. Scientific reports 35 35087187
2019 Inhibition of MCM2 enhances the sensitivity of ovarian cancer cell to carboplatin. Molecular medicine reports 35 31322224
2019 A conserved Mcm4 motif is required for Mcm2-7 double-hexamer formation and origin DNA unwinding. eLife 33 31385807
2011 Oncogenic activity of MCM7 transforming cluster. World journal of clinical oncology 32 21603321
2008 MCM7 interacts with androgen receptor. The American journal of pathology 32 18988800
2022 The structural basis of Cdc7-Dbf4 kinase dependent targeting and phosphorylation of the MCM2-7 double hexamer. Nature communications 31 35614055
2017 RACK1 promotes lung cancer cell growth via an MCM7/RACK1/ Akt signaling complex. Oncotarget 30 28465488
2022 Mcm2 promotes stem cell differentiation via its ability to bind H3-H4. eLife 29 36354740
2013 The ORC/Cdc6/MCM2-7 complex facilitates MCM2-7 dimerization during prereplicative complex formation. Nucleic acids research 29 24234446
2017 The Expression of MCM7 is a Useful Biomarker in the Early Diagnostic of Gastric Cancer. Pathology oncology research : POR 28 28540486
2014 Correlation of MCM2 detection with stage and virology of cervical cancer. The International journal of biological markers 26 24706378
2019 Sir2 suppresses transcription-mediated displacement of Mcm2-7 replicative helicases at the ribosomal DNA repeats. PLoS genetics 25 31083663
2017 Amplified 7q21-22 gene MCM7 and its intronic miR-25 suppress COL1A2 associated genes to sustain intestinal gastric cancer features. Molecular carcinogenesis 25 28059478
2013 Inhibition of DNA binding of MCM2-7 complex by phosphorylation with cyclin-dependent kinases. Journal of biochemistry 25 23864661
2015 Minichromosome maintenance-2 (MCM2) expression differentiates oral squamous cell carcinoma from pre-cancerous lesions. The Malaysian journal of pathology 24 26712671
2014 The role of the MCM2-7 helicase complex during Arabidopsis seed development. Plant molecular biology 24 24947836
2011 GINS and Sld3 compete with one another for Mcm2-7 and Cdc45 binding. The Journal of biological chemistry 24 21362622
2013 Comparison of minichromosome maintenance proteins (MCM-3, MCM-7) and metallothioneins (MT-I/II, MT-III) expression in relation to clinicopathological data in ovarian cancer. Anticancer research 23 24324072
2021 PRMT5 promotes colorectal cancer growth by interaction with MCM7. Journal of cellular and molecular medicine 22 33675123
2010 Transcriptional induction of minichromosome maintenance protein 7 (Mcm7) in human cholangiocarcinoma cells treated with Clonorchis sinensis excretory-secretory products. Molecular and biochemical parasitology 22 20236609
2006 Identification, molecular cloning, and cellular distribution of the rat homolog of minichromosome maintenance protein 7 (MCM7) in the rat testis. Molecular reproduction and development 22 16557521
2019 Resting cells rely on the DNA helicase component MCM2 to build cilia. Nucleic acids research 21 30329080
2018 Proteomic Analysis and NIR-II Imaging of MCM2 Protein in Hepatocellular Carcinoma. Journal of proteome research 21 29750532
2015 Immunohistochemical Evaluation of Minichromosome Maintenance Protein 7 (MCM7), Topoisomerase IIα, and Ki-67 in Diffuse Malignant Peritoneal Mesothelioma Patients Using Tissue Microarray. Annals of surgical oncology 21 25777091
2015 Expression of MCM-3 and MCM-7 in Primary Cutaneous T-cell Lymphomas. Anticancer research 21 26504025
2013 The protein levels of MCM7 and p63 in evaluating lesion severity of cervical disease. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 21 23318911
2021 MCM complex members MCM3 and MCM7 are associated with a phenotypic spectrum from Meier-Gorlin syndrome to lipodystrophy and adrenal insufficiency. European journal of human genetics : EJHG 20 33654309
2018 O-GlcNAc transferase associates with the MCM2-7 complex and its silencing destabilizes MCM-MCM interactions. Cellular and molecular life sciences : CMLS 20 30069701
2008 Colocalization of MCM8 and MCM7 with proteins involved in distinct aspects of DNA replication. Microscopy research and technique 20 18072282
2023 The N-terminus of Spt16 anchors FACT to MCM2-7 for parental histone recycling. Nucleic acids research 19 37850662
2014 Helicase loading: how to build a MCM2-7 double-hexamer. Seminars in cell & developmental biology 19 24637008
2012 Endogenous MCM7 microRNA cluster as a novel platform to multiplex small interfering and nucleolar RNAs for combinational HIV-1 gene therapy. Human gene therapy 19 22834872
2007 Human INT6 interacts with MCM7 and regulates its stability during S phase of the cell cycle. Oncogene 19 17310990
2023 The assembly of the MCM2-7 hetero-hexamer and its significance in DNA replication. Biochemical Society transactions 18 37145026
2021 miR-107 regulates the effect of MCM7 on the proliferation and apoptosis of colorectal cancer via the PAK2 pathway. Biochemical pharmacology 18 34010598
2015 Dpb11 protein helps control assembly of the Cdc45·Mcm2-7·GINS replication fork helicase. The Journal of biological chemistry 18 25659432
2011 Overexpression of MCM2 in myelodysplastic syndromes: association with bone marrow cell apoptosis and peripheral cytopenia. Experimental and molecular pathology 18 22115939
2008 Cleavage of MCM2 licensing protein fosters senescence in human keratinocytes. Cell cycle (Georgetown, Tex.) 18 19001876
2019 BRCA1 represses DNA replication initiation through antagonizing estrogen signaling and maintains genome stability in parallel with WEE1-MCM2 signaling during pregnancy. Human molecular genetics 17 30445628
2016 MCM2 mediates progesterone-induced endometrial stromal cell proliferation and differentiation in mice. Endocrine 17 26910396
2007 Evaluation of AIbZIP and Cdc47 as markers for human prostatic diseases. Urology 17 17270658
2007 Green tea catechins suppress the DNA synthesis marker MCM7 in the TRAMP model of prostate cancer. Molecular oncology 17 18521193
2003 Conditional expression of MCM7 increases tumor growth without altering DNA replication activity. FEBS letters 17 14550576
2023 Regulation of replication origin licensing by ORC phosphorylation reveals a two-step mechanism for Mcm2-7 ring closing. Proceedings of the National Academy of Sciences of the United States of America 16 37428921
2008 Identification and characterization of a rice MCM2 homologue required for DNA replication. BMB reports 16 18755073
2022 Cryo-EM structure of human hexameric MCM2-7 complex. iScience 15 36117988