Affinage

MCM7

DNA replication licensing factor MCM7 · UniProt P33993

Length
719 aa
Mass
81.3 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MCM7 is a core subunit of the MCM2-7 replicative DNA helicase that drives both initiation and elongation of chromosomal DNA replication (PMID:15329670). Within the catalytically active MCM4-MCM6-MCM7 sub-complex, MCM7's conserved ATPase motifs are essential for both ATPase and DNA helicase activity, and isolated MCM7 has no intrinsic activity—it functions only through assembly with partner subunits (PMID:10567526, PMID:12207017). MCM7 is loaded onto chromatin at origins in a regulated manner: SETD3-catalyzed methylation of MCM7 at histidine-459 is required for CDT1-mediated chromatin loading and origin firing (PMID:39455502), and helicase loading and complex assembly are tuned by a cascade of phosphorylation events—cyclin E/CDK2 and cyclin B/CDK1 phosphorylate Ser-121 to control pre-RC assembly and mitotic exit (PMID:23720738), while inhibitory CDK/EBV-PK phosphorylation of MCM4 inactivates the helicase (PMID:17005684). Beyond replication, MCM7 couples origin function to checkpoint signaling: it physically interacts with Rad17 and is required for ATR recruitment and Chk1 phosphorylation after replication stress (PMID:15538388). Its activity is held in check by the retinoblastoma protein, which binds the MCM7 C-terminus and inhibits replication until cyclin D1/CDK4 catalyzes dissociation of the Rb·MCM7 complex from chromatin (PMID:9566894, PMID:12519773). Removal from chromatin at replication termination is achieved by RNF8-catalyzed K63-linked polyubiquitination at K145, linking CMG helicase disassembly to the DNA damage response (PMID:39004272). Numerous proliferative inputs—including cyclin A binding required for S-phase entry (PMID:23720738), the RACK1/Akt scaffold and EGFR→Lyn→Y600 phosphorylation that promote MCM complex assembly (PMID:23313748, PMID:23764002), and transcriptional activation by MYCN and E2F elements in its promoter (PMID:11861392, PMID:9714754)—converge on MCM7 to license proliferation, and biallelic pathogenic MCM7 variants that impair complex formation and S-phase progression cause autosomal recessive primary microcephaly and intellectual disability (PMID:34059554).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1995 High

    Establishing that the MCM7 ortholog cycles between nucleus and cytoplasm in step with replication addressed how helicase availability is restricted to a single round of replication per cycle.

    Evidence Immunofluorescence and subcellular fractionation of yeast Cdc47 with cell cycle staging, plus complementation genetics

    PMID:7708676

    Open questions at the time
    • Did not define the molecular trigger for nuclear import/export
    • Yeast ortholog; human regulation not directly tested here
  2. 1998 High

    Identifying direct Rb binding to the MCM7 C-terminus and its replication-inhibitory consequence revealed a mechanism coupling cell-cycle control machinery to the replicative helicase.

    Evidence Yeast two-hybrid, in vitro binding, Co-IP, and Xenopus in vitro replication assay

    PMID:9566894

    Open questions at the time
    • Did not show how Rb·MCM7 is relieved in vivo
    • Effect on helicase enzymatic activity not directly measured
  3. 1999 High

    Reconstitution of the MCM4-6-7 sub-complex demonstrated that the MCM proteins possess intrinsic helicase activity and that distinct subunits supply ATPase versus ssDNA-binding functions.

    Evidence In vitro helicase assay with purified recombinant complexes and ATPase-motif mutagenesis of MCM4/MCM6

    PMID:10567526

    Open questions at the time
    • MCM7's specific catalytic contribution not yet defined
    • Did not address the full MCM2-7 hexamer
  4. 2002 High

    Mutagenesis showed MCM7's conserved ATPase motifs are essential for the sub-complex's helicase activity and that MCM7 has no activity alone, establishing MCM7 as a catalytically integral but assembly-dependent subunit.

    Evidence In vitro ATPase/helicase assays, site-directed mutagenesis of MCM7 motifs, gel filtration

    PMID:12207017

    Open questions at the time
    • Structural basis of inter-subunit cooperation not resolved
    • Role within intact MCM2-7 not tested
  5. 2004 High

    Functional neutralization in cell-free extracts established the MCM2-7 complex (via MCM7) as the replicative helicase active during elongation, not only initiation.

    Evidence Xenopus egg extract replication assay with Rb(1-400) and anti-Cdc45 inhibition plus aphidicolin uncoupling

    PMID:15329670

    Open questions at the time
    • Did not define Cdc45's biochemical role in the active helicase
    • Mammalian cell-based confirmation not provided
  6. 2004 High

    Discovery of the MCM7–Rad17 interaction connected origin licensing machinery to ATR-dependent S-phase checkpoint signaling.

    Evidence Co-IP, siRNA depletion, ATR foci immunofluorescence, and phospho-Chk1 immunoblotting

    PMID:15538388

    Open questions at the time
    • Did not resolve whether MCM7's checkpoint role is separable from its helicase role
    • Direct binding interface not mapped
  7. 2010 High

    Reciprocal genetic suppression with matched cyclin A and MCM7 mutants demonstrated that a direct cyclin A–MCM7 interaction on chromatin is required for S-phase entry.

    Evidence Cyclin A/MCM7 interaction mutants, chromatin-fraction Co-IP, RNAi rescue, S-phase assays

    PMID:21078875

    Open questions at the time
    • Whether cyclin A delivers CDK activity to MCM7 not established
    • Phosphorylation target on MCM7 not identified here
  8. 2013 High

    Mapping CDK phosphorylation of MCM7 at Ser-121 defined a switch governing both pre-RC assembly and mitotic exit.

    Evidence In vitro CDK kinase assays, S121A mutagenesis, inducible overexpression, pre-RC Co-IP, cell cycle analysis

    PMID:23720738

    Open questions at the time
    • In vivo stoichiometry and timing of S121 phosphorylation not quantified
    • Structural effect of phosphorylation on assembly unknown
  9. 2013 High

    The EGFR→Lyn→MCM7 Y600 cascade and the RACK1/Akt scaffold showed how growth-factor and oncogenic signaling directly enhance MCM complex assembly and licensing.

    Evidence In vitro kinase assays, phospho-specific antibodies, Co-IP, RACK1 binding mutants, chromatin fractionation, and transformation assays

    PMID:23313748 PMID:23764002

    Open questions at the time
    • How phosphorylation mechanistically strengthens inter-subunit contacts unknown
    • Crosstalk between Y600 and Akt phosphosites not addressed
  10. 2021 High

    Identification of biallelic MCM7 variants in patients linked impaired MCM complex formation and S-phase progression to a Mendelian neurodevelopmental disorder.

    Evidence Exome/genome sequencing, complex-formation and S-phase assays, and wild-type vs mutant rescue in neuroblastoma cells

    PMID:34059554

    Open questions at the time
    • Tissue-specific basis of microcephaly phenotype not explained
    • Variant effect on helicase catalysis not directly measured
  11. 2024 High

    Discovery of SETD3-mediated H459 methylation, RIOK2 phosphorylation, and RNF8 K63 ubiquitination at K145 defined the post-translational code controlling MCM7 chromatin loading and termination-coupled unloading.

    Evidence In vitro methylation/kinase/ubiquitination assays with site mutagenesis, NS-seq origin mapping, CDT1 chromatin-loading assays, and cell-cycle-staged fractionation

    PMID:38117512 PMID:39004272 PMID:39455502

    Open questions at the time
    • Interplay/ordering among these modifications not integrated
    • How K145 ubiquitination triggers CMG disassembly mechanistically unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse PTMs, partner interactions, and transcriptional inputs on MCM7 are temporally coordinated into a single regulated licensing-to-unloading cycle remains unresolved.
  • No integrated structural model of MCM7 within the loaded vs active CMG helicase from this corpus
  • Non-canonical roles (e.g., autophagy, centrosome splitting) lack mechanistic integration with replication function

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 3 GO:0003677 DNA binding 2 GO:0140657 ATP-dependent activity 2 GO:0003924 GTPase activity 1
Localization
GO:0000228 nuclear chromosome 4 GO:0005634 nucleus 2 GO:0005815 microtubule organizing center 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-69306 DNA Replication 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1640170 Cell Cycle 2 R-HSA-8953897 Cellular responses to stimuli 1
Partners
CCNA (CYCLIN A)CDT1MCM4MCM6RACK1RAD17RB1RNF8
Complex memberships
MCM2-7 helicaseMCM4-MCM6-MCM7 sub-complexpre-replication complex

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 The MCM4-MCM6-MCM7 complex has intrinsic DNA helicase activity. Mutation of conserved ATPase motifs in MCM6 abolished helicase activity, indicating MCM6 ATP binding is critical. MCM4 contributes to single-stranded DNA binding activity of the complex, and these two activities (helicase and ssDNA binding) can be separated. In vitro helicase assay with purified recombinant complexes from insect cells; ATPase motif mutagenesis of MCM4 and MCM6 Molecular and cellular biology High 10567526
2002 Conserved ATPase motifs of MCM7 are essential for both ATPase and DNA helicase activities of the MCM4/6/7 complex. Uncomplexed MCM7 alone displays neither ATPase nor DNA helicase activity, indicating MCM7 contributes to helicase activity only through interaction with other subunits. A zinc finger mutant of MCM4 with impaired DNA binding showed elevated helicase activity and tended to dissociate into trimeric complexes, suggesting MCM4 zinc finger is involved in subunit interactions. In vitro ATPase and DNA helicase assays; site-directed mutagenesis of MCM7 ATPase motifs and MCM4 zinc finger; gel filtration analysis of complex assembly The Journal of biological chemistry High 12207017
2004 MCM7 and CDC45 are required throughout DNA replication elongation in vertebrates, not just initiation. Neutralization of MCM7 using an Rb(1-400) fragment and Cdc45 antibodies both abolished chromosome unwinding by the uncoupled helicase (in aphidicolin-treated extracts), providing direct evidence that the MCM2-7 complex is the replicative DNA helicase and that Cdc45 is a helicase co-factor. Xenopus egg extract DNA replication assay; functional inhibition with Rb(1-400) fragment and anti-Cdc45 antibodies; aphidicolin-induced helicase uncoupling assay The EMBO journal High 15329670
1998 The retinoblastoma protein (Rb) directly interacts with MCM7 via the Rb amino-terminus (residues 1-400) binding the C-terminal 137 amino acids of MCM7. Rb-related proteins p107 and p130 also bind MCM7. The Rb amino-terminus strongly inhibited DNA replication in an MCM7-dependent fashion in a Xenopus in vitro replication assay, establishing that Rb negatively regulates DNA replication through direct interaction with MCM7. Yeast two-hybrid screen; in vitro binding assay; anti-Rb co-immunoprecipitation from human cells; Xenopus in vitro DNA replication assay Molecular and cellular biology High 9566894
1995 Yeast Cdc47 (MCM7 ortholog) undergoes cell cycle-regulated nuclear import and export: it enters the nucleus at mitosis, remains there until the initiation of DNA replication, then is rapidly exported to the cytoplasm at the start of S phase. Cdc47 protein levels do not vary with the cell cycle but expression and nascent synthesis peak in late M phase. Indirect immunofluorescence microscopy; subcellular fractionation; CDC47 gene isolation by complementation of temperature-sensitive mutant Proceedings of the National Academy of Sciences of the United States of America High 7708676
2004 Human MCM7 physically interacts with hRad17 and is required for replication checkpoint signaling. Depletion of either hRad17 or hMCM7 by siRNA suppressed UV- or aphidicolin-induced Chk1 phosphorylation and abolished UV-induced S-phase checkpoint activation. MCM7-depleted cells were defective for ATR nuclear foci formation after UV irradiation, indicating MCM7 is required for stable ATR recruitment to damaged DNA. Co-immunoprecipitation to identify hMCM7 as hRad17-interacting protein; siRNA knockdown; immunofluorescence for ATR foci; phospho-Chk1 immunoblotting The EMBO journal High 15538388
2003 Cyclin D1/CDK4 binds to MCM7 and MCM3 in the pre-replication complex on chromatin. Active cyclin D1/CDK4 catalyzes dissociation of the RB·MCM7 complex and promotes removal of RB from chromatin-bound complexes, although cyclin D1/CDK4 does not phosphorylate MCM7 directly. Cyclin E/CDK2 did not replicate this effect. Co-immunoprecipitation; chromatin fractionation; in vitro kinase assay; RB·MCM7 complex dissociation assay The Journal of biological chemistry High 12519773
2006 Phosphorylation of MCM4 at Thr-19 and Thr-110 by CDK2/CDK1 inactivates the MCM4-MCM6-MCM7 helicase activity. EBV protein kinase (EBV-PK) phosphorylates these same sites plus additional sites on MCM4 and MCM6, also inactivating helicase activity. This mechanism accounts for blockade of chromosomal DNA replication during EBV lytic replication. In vitro helicase assay with purified MCM4-6-7 complex; phosphorylation site mapping; site-directed mutagenesis of MCM4 N-terminal Ser/Thr residues; EBV-PK expression in HeLa cells Journal of virology High 17005684
2005 Polo-like kinase 1 (Plk1) interacts with MCM7 (and other MCM2-7 complex members) via its polo-box domain. Endogenous Plk1 co-immunoprecipitates with both basal and DNA damage-induced slower-migrating forms of Mcm7. The strongest interaction is in the soluble chromatin fraction, suggesting Plk1 coordinates DNA replication and mitotic events at chromatin. Polo-box domain pulldown screen; co-immunoprecipitation of endogenous proteins; subcellular fractionation (chromatin fraction) The Journal of biological chemistry Medium 15654075
2010 Cyclin A promotes S-phase entry through direct interaction with MCM7. A cyclin A mutant (CycA-C1) that cannot bind MCM7 fails to promote S-phase entry. An Mcm7 mutant (Mcm7-3) that can bind CycA-C1 suppresses the S-phase entry defect of CycA-C1. Cyclin A and Mcm7 interact specifically in the chromatin fraction. Cyclin A mutant derivation; Mcm7 interaction screen; co-immunoprecipitation from chromatin fraction; RNAi knockdown and mutant rescue experiments; S-phase entry assays Molecular and cellular biology High 21078875
2013 MCM7 is phosphorylated at Ser-121 by cyclin E/CDK2 and cyclin B/CDK1. The MCM7-S121A mutant fails to efficiently form a pre-RC complex with MCM3/MCM5/Cdc45. Overexpression of wild-type MCM7 (but not S121A) blocks S-phase entry through activation of the Chk1/p53 checkpoint. MCM7-S121A overexpression causes M-phase exit delay, indicating that Ser-121 phosphorylation in M phase is important for proper mitotic exit. In vitro kinase assay (cyclin E/CDK2, cyclin B/CDK1); site-directed mutagenesis (S121A); Tet-On inducible overexpression; co-immunoprecipitation for pre-RC complex; cell cycle analysis; Chk1 phosphorylation western blot The Journal of biological chemistry High 23720738
2013 Activated EGFR phosphorylates the p56 isoform of Lyn at Y32, which then phosphorylates MCM7 at Y600, increasing MCM7 association with other MCM complex proteins, thereby promoting DNA synthesis complex assembly and cell proliferation. Biochemical signaling cascade analysis; phospho-specific antibodies; co-immunoprecipitation; in vitro kinase assays; knockdown/overexpression in cancer cell lines Cancer cell High 23764002
2005 The CDK inhibitor p27Kip1 directly binds the conserved MCM domain of MCM7. This interaction occurs in a growth factor-dependent manner in vivo. The C-terminal domain of p27Kip1 inhibits DNA replication through this MCM7 interaction, independently of its function as a CDK inhibitor. Co-immunoprecipitation; in vitro binding assay; domain mapping; DNA replication assay with C-terminal p27Kip1 domain FEBS letters Medium 16289477
2008 MCM7 physically interacts with the androgen receptor (AR) both in vitro and in vivo. The AR-binding motif in MCM7 maps to amino acids 221-248, and the MCM7-binding motif in AR maps to amino acids 426-475. High doses of androgen (R1881) decreased MCM7 binding to genomic DNA, reduced DNA synthesis, and decreased S-phase entry; low doses increased MCM7 DNA licensing activity and proliferation. The MCM7/AR interaction down-regulated MCM7 expression, and AR transcriptional activity depended on its interaction with MCM7. Co-immunoprecipitation in vitro and in vivo; domain mapping by deletion mutants; DNA synthesis assay; FACS cell cycle analysis; MCM7 knockdown; AR mutant defective in MCM7 binding The American journal of pathology High 18988800
2007 Human INT6 interacts with MCM7, and INT6 stabilizes chromatin-bound MCM7 protein. Proteasome inhibition strengthens the INT6–MCM7 interaction. In INT6-silenced cells, removal of MCM7 from chromatin during replication is accelerated, leading to reduced thymidine incorporation and reinforced RPA and claspin chromatin association, indicating replication deficiency. Yeast two-hybrid (INT6 as bait); co-immunoprecipitation; proteasome inhibitor treatment; chromatin fractionation; thymidine incorporation assay; siRNA depletion Oncogene Medium 17310990
2000 MAT1, the CDK-activating kinase assembly/targeting factor, physically interacts with MCM7. The C-terminal domain of MAT1 is required for this interaction (the RING finger is dispensable). MCM7 associates with the CAK complex in vivo in human osteosarcoma cells. Yeast two-hybrid screen; in vitro protein binding assay; co-immunoprecipitation from human MG63 cells FEBS letters Medium 11056214
2003 In S. cerevisiae, Mcm7 acts as a novel cofactor of Mcm1 to modulate its own expression. Mcm7 stimulates Mcm1 binding to the early cell cycle box (ECB) upstream of the MCM7, CDC6, and MCM5 promoters. Mcm7 is recruited to these promoters during late M phase, consistent with a direct role in regulating periodic expression of early cell cycle genes. Genetic analysis (mcm7-1 and mcm1-1 mutants); chromatin immunoprecipitation; in vitro DNA binding (Mcm1 binding stimulation by Mcm7); promoter reporter assays The Journal of biological chemistry Medium 12738768
2001 In S. pombe, mcm7+ is essential for viability; loss of mcm7+ causes delayed S-phase entry and arrest with 2C DNA content. Mcm7p is a nuclear protein throughout the cell cycle, and its nuclear localization depends on the other MCM proteins. mcm7-98 is synthetically lethal with checkpoint mutants (Δcds1, Δchk1, Δrad3), suggesting chromosomal defects even at permissive temperature. Genetic evidence suggests the Mcm3p-Mcm5p dimer interacts with the Mcm4p-Mcm6p-Mcm7p core through Mcm7p. Genetic complementation; spore viability analysis; flow cytometry; immunofluorescence localization; synthetic lethality screens with checkpoint mutants Genetics Medium 11606526
2013 RACK1 interacts with MCM7 (binding motif at amino acids 221-248 of MCM7) and acts as a scaffold bringing Akt into proximity with MCM7. RACK1 overexpression increases Akt-dependent MCM7 phosphorylation, promotes MCM7 chromatin binding and MCM complex formation, thereby stimulating DNA replication. PKC activation by PMA redistributes RACK1 from nucleus to cytoplasm, decreasing MCM7 chromatin association and inducing growth arrest. An MCM7 mutant unable to bind RACK1 lacks DNA replication licensing and oncogenic transformation activity. Co-immunoprecipitation in vivo and in vitro; domain mapping; RACK1 knockdown; PKC activation; chromatin fractionation; DNA synthesis assay; oncogenic transformation assay The American journal of pathology High 23313748
2017 RACK1 mediates MCM7 phosphorylation by Akt in a ternary MCM7/RACK1/Akt signaling complex, increasing MCM7 chromatin binding and MCM complex formation to promote DNA replication and cell proliferation in non-small-cell lung cancer. Co-immunoprecipitation; overexpression; in vitro phosphorylation assay; chromatin fractionation; cell proliferation assays Oncotarget Medium 28465488
2019 ATO suppresses MCM7 transcription by targeting the SRF/MCM7 complex, which functions as a transcriptional regulator of MCM7 expression in HCC. MCM7 knockdown recapitulates ATO effects on cancer stem cell traits and metastasis, while MCM7 overexpression abolishes these effects. Co-immunoprecipitation/complex identification; MCM7 promoter assays; MCM7 knockdown and overexpression; in vivo xenograft and metastasis models Cell death & disease Medium 31186405
2002 MYCN directly transcriptionally activates MCM7 in neuroblastoma. Induction of MYCN increases endogenous MCM7 mRNA and protein levels (~3-fold). MCM7 promoter/luciferase reporter activity is significantly increased under MYCN-induced conditions, and specific EMSA shifts of MCM7 promoter sequences are detected in MYCN-amplified cell extracts. Microarray analysis; conditional MYCN induction; luciferase reporter assay; electrophoretic mobility shift assay (EMSA); western blot Cancer research Medium 11861392
1998 The human MCM7 promoter contains functional E2F binding sites and an E-box that are essential for promoter activity. Multiple transcription start sites are used upon growth stimulation. The minimal promoter requires an E-box and one E2F site for transcription. Promoter cloning; luciferase reporter assays; deletion analysis; identification of transcription start sites Gene Medium 9714754
2021 Biallelic pathogenic variants in MCM7 cause autosomal recessive primary microcephaly and intellectual disability. Variants in MCM7 interfere with MCM complex formation and impair S-phase progression efficiency. The p.A265T missense variant is deleterious; overexpression of wild-type but not mutant MCM7 counterbalances the reduced cell viability/proliferation caused by Mcm7 knockdown in neuroblastoma cells. Exome/genome sequencing; functional studies: MCM complex formation assay; S-phase progression analysis; Mcm7 knockdown in mouse neuroblastoma cells; wild-type vs. mutant MCM7 rescue experiment Journal of medical genetics High 34059554
2017 MCM7 depletion promotes mitotic exit by inhibiting CDK1 activity. MCM7 maintains chromatin association during M phase. MCM7 siRNA depletion leads to CDK1 inactivation, promotes cohesin/RAD21 cleavage, and accelerates sister chromatid segregation. MCM7 co-localizes with tubulin in mitotic cells and its depletion results in aberrant spindle formation. siRNA knockdown; CDK1 activity assay; cohesin/RAD21 cleavage immunoblot; immunofluorescence co-localization with tubulin; cell cycle analysis Scientific reports Medium 28588300
2017 MCM7 overexpression strengthens the Cep68-VHL interaction at centrosomes, leading to Cep68 ubiquitination and proteasomal degradation, thereby causing centrosome splitting. MCM7 directly binds Cep68 in vitro and complexes with Cep68 and VHL in vivo. Absence of MCM7 weakens the Cep68-VHL interaction. In vitro binding assay (MCM7 with Cep68); co-immunoprecipitation (MCM7/Cep68/VHL); overexpression and knockdown; ubiquitination assay; immunofluorescence for centrosome splitting Biochemical and biophysical research communications Medium 28578000
2024 SETD3 histidine methyltransferase methylates MCM7 at histidine-459 (H459me), and this modification is required for CDT1-mediated chromatin loading of the MCM complex and for replication origin firing. SETD3 depletion attenuates early replication origin firing. CDK2 phosphorylates SETD3 at Ser-21 during G1/S, which is required for this pathway. Impairment of H459 methylation on MCM7 attenuates DNA synthesis and MCM chromatin loading. Nascent-strand sequencing (NS-seq) for replication origin analysis; biochemical pulldown (SETD3 binds MCM); in vitro methylation assay (SETD3 on MCM7 H459); site-directed mutagenesis (H459A); CDT1-mediated chromatin loading assay; CDK2 phosphorylation of SETD3 Science China. Life sciences High 39455502
2024 PLCE1 promotes MCM7 expression via PKCα-mediated phosphorylation of E2F1, which transcriptionally activates MCM7. Additionally, PLCE1 potentiates phosphorylation of MCM7 at six threonine residues by the atypical kinase RIOK2, promoting MCM complex assembly and chromatin loading. Inhibition of PLCE1 or RIOK2 impairs MCM7-mediated DNA replication, causing G1-S arrest. Phosphorylation site mapping (six Thr residues); kinase assay (RIOK2 on MCM7); MCM complex assembly co-immunoprecipitation; chromatin loading assay; E2F1 phosphorylation analysis; cell cycle assays; in vivo tumor models Cancer research High 38117512
2024 The E3 ubiquitin ligase RNF8 catalyzes K63-linked multi-ubiquitination of MCM7 at K145, both in vitro and in vivo. This modification is dynamically regulated during the cell cycle, peaking on chromatin during late S phase. RNF168 and BRCA1 promote MCM7 polyubiquitylation during replication termination. Upon DNA damage, RNF8-mediated MCM7 polyubiquitination decreases significantly during late S phase, linking CMG helicase disassembly to DNA damage response. In vitro ubiquitination assay (RNF8 on MCM7); in vivo ubiquitination assay; K145 site mapping; cell cycle-staged chromatin fractionation; RNF168/BRCA1 co-transfection assays; DNA damage treatment Life sciences High 39004272
2021 PRMT5 physically interacts with MCM7; the direct binding domain in MCM7 maps to residues 1-248. Co-immunoprecipitation confirmed the physical interaction. MCM7 promotes CRC cell proliferation, migration, and invasion in vitro. Co-immunoprecipitation; domain mapping (MCM7 deletion constructs); siRNA/overexpression functional assays in CRC cells Journal of cellular and molecular medicine Medium 33675123
2022 MCM7 facilitates autolysosome formation by binding dynein, thereby promoting autophagic flux in bladder cancer stem-like cells. MCM7 knockdown inhibits autophagic flux, reduces stemness, and triggers AMPK activation leading to increased BCL2/BECLIN1 interaction and P53 accumulation. MCM7 knockdown; co-immunoprecipitation (MCM7 with dynein); autophagy/mitophagy flux assays; AMPK pathway analysis; mitochondrial respiration measurement iScience Medium 36111256
2025 Histone lactylation at the MCM7 locus facilitates MCM7 transcriptional activation in hepatocellular carcinoma. Treatment with glycolysis inhibitor 2-DG decreases MCM7 mRNA and protein, while rotenone (glycolysis activator) increases them. Rescue experiments confirmed histone lactylation is necessary for MCM7-driven CSC properties and radio-resistance. 2-DG and rotenone treatment; MCM7 knockdown/overexpression; spheroid formation assays; colony formation; xenograft model; rescue experiments with histone lactylation modulation Biochemical pharmacology Medium 40118288
2024 E2F8 transcription factor binds the MCM7 promoter and activates MCM7 transcription. E2F8 knockdown suppresses bladder cancer cell proliferation and causes G1 arrest; MCM7 overexpression rescues these effects, placing E2F8 upstream of MCM7 in bladder cancer cell cycle regulation. Chromatin immunoprecipitation (E2F8 binding to MCM7 promoter); luciferase reporter assay; E2F8 knockdown; MCM7 overexpression rescue; in vivo xenograft model Biochemistry and cell biology Medium 39601318
2024 Splicing factor WBP11, whose transcription is activated by FOXM1, represses intron 4 retention in MCM7 pre-mRNA, thereby maintaining MCM7 expression. WBP11 silencing decreases MCM7 expression via increased intron 4 retention, and MCM7 knockdown attenuates the malignant behaviors promoted by WBP11 overexpression in ovarian cancer. RNA-seq with alternative splicing analysis; WBP11 siRNA knockdown; FOXM1 ChIP at WBP11 promoter; MCM7 overexpression rescue; in vitro and in vivo functional assays Oncogene Medium 38561505
2010 In cholangiocarcinoma cells, C. sinensis excretory-secretory products increase global histone acetylation and recruit histone acetyltransferases (HATs) to the MCM7 promoter, leading to transcriptional activation of MCM7. ChIP assays confirmed HAT recruitment to the MCM7 promoter under ESP treatment. Promoter reporter assays; chromatin immunoprecipitation (HAT recruitment); histone acetylation assays; ChIP Molecular and biochemical parasitology Medium 20236609

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
2004 A requirement for MCM7 and Cdc45 in chromosome unwinding during eukaryotic DNA replication. The EMBO journal 207 15329670
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
2006 MCM7 amplification and overexpression are associated with prostate cancer progression. Oncogene 161 16247466
1995 Cell cycle-regulated nuclear import and export of Cdc47, a protein essential for initiation of DNA replication in budding yeast. Proceedings of the National Academy of Sciences of the United States of America 120 7708676
2014 Histone deacetylase inhibitor SAHA epigenetically regulates miR-17-92 cluster and MCM7 to upregulate MICA expression in hepatoma. British journal of cancer 104 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 99 16518415
2014 Juvenile hormone-receptor complex acts on mcm4 and mcm7 to promote polyploidy and vitellogenesis in the migratory locust. PLoS genetics 95 25340846
2004 Interaction between human MCM7 and Rad17 proteins is required for replication checkpoint signaling. The EMBO journal 92 15538388
2012 miR-93/106b and their host gene, MCM7, are differentially expressed in leiomyomas and functionally target F3 and IL-8. Molecular endocrinology (Baltimore, Md.) 91 22556343
2004 DNA replication regulation protein Mcm7 as a marker of proliferation in prostate cancer. Journal of clinical pathology 81 15452160
2002 Minichromosome maintenance protein MCM7 is a direct target of the MYCN transcription factor in neuroblastoma. Cancer research 76 11861392
2003 The cyclin D1-dependent kinase associates with the pre-replication complex and modulates RB.MCM7 binding. The Journal of biological chemistry 75 12519773
2016 MCM4 and MCM7, potential novel proliferation markers, significantly correlated with Ki-67, Bmi1, and cyclin E expression in esophageal adenocarcinoma, squamous cell carcinoma, and precancerous lesions. Human pathology 64 27476776
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
2019 Arsenic trioxide inhibits liver cancer stem cells and metastasis by targeting SRF/MCM7 complex. Cell death & disease 59 31186405
2013 Epidermal growth factor receptor potentiates MCM7-mediated DNA replication through tyrosine phosphorylation of Lyn kinase in human cancers. Cancer cell 57 23764002
2016 Upregulated expression of BCL2, MCM7, and CCNE1 indicate cisplatin-resistance in the set of two human bladder cancer cell lines: T24 cisplatin sensitive and T24R2 cisplatin resistant bladder cancer cell lines. Investigative and clinical urology 55 26966728
2006 Phosphorylation of MCM4 at sites inactivating DNA helicase activity of the MCM4-MCM6-MCM7 complex during Epstein-Barr virus productive replication. Journal of virology 55 17005684
2016 MCM7 and its hosted miR-25, 93 and 106b cluster elicit YAP/TAZ oncogenic activity in lung cancer. Carcinogenesis 54 27797825
2005 Replicative MCM7 protein as a proliferation marker in endometrial carcinoma: a tissue microarray and clinicopathological analysis. Histopathology 52 15720416
2008 Expression of Mcm7 and Cdc6 in oral squamous cell carcinoma and precancerous lesions. Anticancer research 51 19189662
1998 Cloning and characterization of human MCM7 promoter. Gene 50 9714754
2017 Simvastatin suppresses the DNA replication licensing factor MCM7 and inhibits the growth of tamoxifen-resistant breast cancer cells. Scientific reports 45 28150753
2005 Interaction of chromatin-associated Plk1 and Mcm7. The Journal of biological chemistry 45 15654075
2009 Dynamic localization of the DNA replication proteins MCM5 and MCM7 in plants. Plant physiology 44 19357199
2003 Mcm7, a subunit of the presumptive MCM helicase, modulates its own expression in conjunction with Mcm1. The Journal of biological chemistry 43 12738768
2001 Characterization of Schizosaccharomyces pombe mcm7(+) and cdc23(+) (MCM10) and interactions with replication checkpoints. Genetics 42 11606526
2022 Oxidative stress-induced circKIF18A downregulation impairs MCM7-mediated anti-senescence in intervertebral disc degeneration. Experimental & molecular medicine 38 35332256
2017 Simvastatin and Atorvastatin inhibit DNA replication licensing factor MCM7 and effectively suppress RB-deficient tumors growth. Cell death & disease 38 28300827
2017 Increased expression of the microRNA 106b~25 cluster and its host gene MCM7 in corticotroph pituitary adenomas is associated with tumor invasion and Crooke's cell morphology. Pituitary 38 28432562
2010 Cyclin A promotes S-phase entry via interaction with the replication licensing factor Mcm7. Molecular and cellular biology 38 21078875
2022 Bioinformatics approaches identified dasatinib and bortezomib inhibit the activity of MCM7 protein as a potential treatment against human cancer. Scientific reports 36 35087187
2013 Phosphorylation of minichromosome maintenance protein 7 (MCM7) by cyclin/cyclin-dependent kinase affects its function in cell cycle regulation. The Journal of biological chemistry 34 23720738
2017 MCM7 amplification and overexpression promote cell proliferation, colony formation and migration in esophageal squamous cell carcinoma by activating the AKT1/mTOR signaling pathway. Oncology reports 33 28498460
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
2017 RACK1 promotes lung cancer cell growth via an MCM7/RACK1/ Akt signaling complex. Oncotarget 30 28465488
2017 The Expression of MCM7 is a Useful Biomarker in the Early Diagnostic of Gastric Cancer. Pathology oncology research : POR 28 28540486
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
2017 Breviscapine (BVP) inhibits prostate cancer progression through damaging DNA by minichromosome maintenance protein-7 (MCM-7) modulation. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 25 28628830
2022 Targeted inhibition of the expression of both MCM5 and MCM7 by miRNA-214 impedes DNA replication and tumorigenesis in hepatocellular carcinoma cells. Cancer letters 23 35490917
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 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 22 33654309
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
2005 The cell cycle regulator p27Kip1 interacts with MCM7, a DNA replication licensing factor, to inhibit initiation of DNA replication. FEBS letters 22 16289477
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
2013 Examining new phylogenetic markers to uncover the evolutionary history of early-diverging fungi: comparing MCM7, TSR1 and rRNA genes for single- and multi-gene analyses of the Kickxellomycotina. Persoonia 20 24027350
2008 Colocalization of MCM8 and MCM7 with proteins involved in distinct aspects of DNA replication. Microscopy research and technique 20 18072282
2024 The splicing factor WBP11 mediates MCM7 intron retention to promote the malignant progression of ovarian cancer. Oncogene 19 38561505
2012 A comparative proteomic study identified LRPPRC and MCM7 as putative actors in imatinib mesylate cross-resistance in Lucena cell line. Proteome science 19 22458888
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
2021 miR-107 regulates the effect of MCM7 on the proliferation and apoptosis of colorectal cancer via the PAK2 pathway. Biochemical pharmacology 18 34010598
2021 MCM2-7 in Clear Cell Renal Cell Carcinoma: MCM7 Promotes Tumor Cell Proliferation. Frontiers in oncology 18 34993142
2019 MCM7 silencing promotes cutaneous melanoma cell autophagy and apoptosis by inactivating the AKT1/mTOR signaling pathway. Journal of cellular biochemistry 18 31535400
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
2007 Histomorphometry and expression of Cdc47 and caspase-3 in hyperthyroid rat uteri and placentas during gestation and postpartum associated with fetal development. Reproduction, fertility, and development 16 17394799
2015 High expression of carbonic anhydrase IX is significantly associated with glandular lesions in gastroesophageal junction and with tumorigenesis markers BMI1, MCM4 and MCM7. BMC gastroenterology 15 26156831
2013 Interaction of MCM7 and RACK1 for activation of MCM7 and cell growth. The American journal of pathology 15 23313748
2022 MCM7 supports the stemness of bladder cancer stem-like cells by enhancing autophagic flux. iScience 14 36111256
2018 Molecular characterization of minichromosome maintenance protein (MCM7) in Scylla paramamosain and its role in white spot syndrome virus and Vibrio alginolyticus infection. Fish & shellfish immunology 14 30205202
2016 MCM7 expression is a promising predictor of recurrence in patients surgically resected for meningiomas. Journal of neuro-oncology 14 27868157
2000 The MAT1 cyclin-dependent kinase-activating kinase (CAK) assembly/targeting factor interacts physically with the MCM7 DNA licensing factor. FEBS letters 14 11056214
1996 Cloning of a cDNA encoding a human homologue of CDC47, a member of the MCM family. Biochimica et biophysica acta 14 8652665
2021 Computational Screening of Natural Compounds for Identification of Potential Anti-Cancer Agents Targeting MCM7 Protein. Molecules (Basel, Switzerland) 13 34641424
2011 Ki-67 and minichromosome maintenance-7 (MCM7) expression in canine pituitary corticotroph adenomas. Domestic animal endocrinology 13 21982272
2025 Histone lactylation facilitates MCM7 expression to maintain stemness and radio-resistance in hepatocellular carcinoma. Biochemical pharmacology 12 40118288
2015 Cantharidin modulates the E2F1/MCM7-miR-106b-93/p21-PTEN signaling axis in MCF-7 breast cancer cells. Oncology letters 12 26722252
2014 ORC1/CDC6 and MCM7 distinct associate with chromatin through Trypanosoma cruzi life cycle. Molecular and biochemical parasitology 12 24681203
1998 cDNA cloning and expression during development of Drosophila melanogaster MCM3, MCM6 and MCM7. Gene 12 9795205
2022 NOL6 Regulates the Proliferation and Apoptosis of Gastric Cancer Cells via Regulating TP53I3, CDK4 and MCM7 Expression. Frontiers in oncology 11 35494047
2014 Differential regulation of MCM7 and its intronic miRNA cluster miR-106b-25 during megakaryopoiesis induced polyploidy. RNA biology 11 25483046
1995 Sequence of mouse CDC47, a member of the minichromosome maintenance (Mcm) family involved in the DNA replication licensing system. Gene 11 8566808
2021 CDC45 modulates MCM7 expression and inhibits cell proliferation by suppressing the PI3K/AKT pathway in acute myeloid leukemia. American journal of translational research 10 34650692
2021 MCM7 affects the cisplatin resistance of liver cancer cells and the development of liver cancer by regulating the PI3K/Akt signaling pathway. Immunopharmacology and immunotoxicology 10 34821526
2017 RNAi-mediated knockdown of MCM7 gene on CML cells and its therapeutic potential for leukemia. Medical oncology (Northwood, London, England) 10 28058629
2012 Unique pattern of ORC2 and MCM7 localization during DNA replication licensing in the mouse zygote. Biology of reproduction 10 22674395
2024 Phospholipase PLCE1 Promotes Transcription and Phosphorylation of MCM7 to Drive Tumor Progression in Esophageal Cancer. Cancer research 9 38117512
2017 Centrosomal MCM7 strengthens the Cep68-VHL interaction and excessive MCM7 leads to centrosome splitting resulting from increase in Cep68 ubiquitination and proteasomal degradation. Biochemical and biophysical research communications 7 28578000
2017 Pre-RC Protein MCM7 depletion promotes mitotic exit by Inhibiting CDK1 activity. Scientific reports 7 28588300
2021 MCM7 as a marker of postsurgical progression in non-functioning pituitary adenomas. European journal of endocrinology 6 33524001
2021 Homozygous mutation in MCM7 causes autosomal recessive primary microcephaly and intellectual disability. Journal of medical genetics 6 34059554
2013 MCM7 expression is altered in rat after spinal cord injury. Journal of molecular neuroscience : MN 5 23526403
2022 High-Throughput Screening and Molecular Dynamics Simulation of Natural Products for the Identification of Anticancer Agents against MCM7 Protein. Applied bionics and biomechanics 4 36157125
2021 Immunohistochemical evaluation of D2-40, Galectin-3, Maspin and MCM7 expression in palate squamous cell carcinomas. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie 4 34609416
2008 Histomorphometry and expression of CDC-47 and caspase-3 in mammary glands of pregnant female rats with artificial hyperthyroidism. Pathology, research and practice 4 18538947
2024 RNF8-mediated multi-ubiquitination of MCM7: Linking disassembly of the CMG helicase with DNA damage response in human cells. Life sciences 3 39004272
2022 In silico investigation of the role of vitamins in cancer therapy through inhibition of MCM7 oncoprotein. RSC advances 3 36349041
2024 SETD3-mediated histidine methylation of MCM7 regulates DNA replication by facilitating chromatin loading of MCM. Science China. Life sciences 2 39455502
2024 E2F8 facilitates malignant phenotypes of muscle-invasive bladder cancer via increasing MCM7 expression. Biochemistry and cell biology = Biochimie et biologie cellulaire 2 39601318

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