Affinage

MCM3

DNA replication licensing factor MCM3 · UniProt P25205

Length
808 aa
Mass
91.0 kDa
Annotated
2026-04-28
85 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MCM3 is an essential subunit of the MCM2-7 heterohexameric replicative helicase that is loaded onto replication origins during late M/G1 phase to license DNA for a single round of replication per cell cycle. MCM3 undergoes cell cycle-regulated chromatin association controlled by multiple phosphorylation events: CDK1 phosphorylates Ser-112 to promote MCM complex assembly and chromatin loading (PMID:18524952), cyclin E/Cdk2 phosphorylates Thr-722 for chromatin association and S-phase checkpoint signaling (PMID:21965652), Chk1 phosphorylates Ser-205 to negatively regulate replication fork progression (PMID:25809478), and ATM phosphorylates C-terminal sites to redistribute MCM3 from chromatin upon DNA damage (PMID:17244605); the prolyl isomerase Pin1 coordinates phosphorylation-dependent chromatin loading and unloading (PMID:30316783). Its PS1 hairpin (Lys-499) is uniquely essential among MCM subunits for DNA unwinding activity of the reconstituted helicase (PMID:24349215), MCM3AP acetylates chromatin-bound MCM3 to inhibit replication initiation (PMID:11258703, PMID:12226073), the KEAP1-CUL3-RBX1 complex ubiquitylates MCM3 on chromatin (PMID:27621311), and MCM3 competes with NRF2 for KEAP1 binding to modulate antioxidant signaling (PMID:30108253, PMID:41797940). MCM3 is selectively cleaved by caspases during apoptosis, inactivating the replicative helicase during programmed cell death (PMID:9473350).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1991 High

    Establishing that MCM3 functions together with MCM2 in an essential, genetically interacting pathway for DNA replication initiation resolved the question of whether MCM genes operate independently or cooperatively.

    Evidence Double-mutant lethality and overexpression suppression analysis in S. cerevisiae

    PMID:2044961

    Open questions at the time
    • Biochemical nature of MCM2-MCM3 interaction unknown
    • No direct evidence of complex formation at this stage
  2. 1993 High

    Demonstrating cell cycle-regulated nuclear localization and chromatin association of MCM3 (nuclear in late M through G1, released in S phase) established the concept that MCM proteins enforce once-per-cycle replication control through regulated chromatin binding.

    Evidence Cell cycle fractionation and subnuclear localization in synchronized S. cerevisiae

    PMID:8224843

    Open questions at the time
    • Mechanism of chromatin release during S phase not identified
    • Phosphorylation events controlling localization not yet mapped
  3. 1994 High

    Identifying two distinct phospho-forms of MCM3 with differential chromatin association during S phase provided the first evidence that phosphorylation directly controls MCM3 chromatin dynamics.

    Evidence Fractionation and cell-cycle synchronization of murine cells with phosphorylation-state-specific detection

    PMID:7925275

    Open questions at the time
    • Kinases responsible for phosphorylation unknown
    • Specific phosphosites not mapped
  4. 1995 High

    Reconstitution of MCM3 as a component of the replication licensing factor in Xenopus egg extracts — showing it binds chromatin before nuclear formation and is required for DNA replication — established MCM3 as a core licensing component and revealed a two-step mechanism requiring a cytosolic loading factor.

    Evidence Immunodepletion/add-back in Xenopus egg extracts with sperm chromatin; nuclear envelope permeabilization experiments

    PMID:7758114 PMID:7760938 PMID:8574584

    Open questions at the time
    • Identity of the cytosolic loading factor not resolved
    • Stoichiometry of MCM3 on chromatin not determined
  5. 1997 Medium

    Mapping the MCM3 NLS and showing that cell cycle-specific nuclear accumulation reflects regulated nuclear retention rather than regulated import resolved how MCM3 achieves cell cycle-dependent localization.

    Evidence NLS mutagenesis with beta-galactosidase reporter fusion and cell cycle analysis in S. cerevisiae

    PMID:9285827 PMID:9427284

    Open questions at the time
    • Retention mechanism not molecularly defined
    • Chromatin-independent retention factors unknown
  6. 1998 Medium

    Identification of Map80/MCM3AP as an MCM3-interacting protein that facilitates nuclear localization, and selective caspase cleavage of MCM3 during apoptosis, expanded the regulatory network around MCM3 beyond cell cycle kinases.

    Evidence Yeast two-hybrid, co-IP, NLS mutagenesis for Map80; caspase inhibitor treatment across multiple apoptosis models for cleavage

    PMID:9473350 PMID:9712829

    Open questions at the time
    • Map80 binding validated in single lab
    • Caspase cleavage site on MCM3 not precisely mapped
    • Physiological consequence of cleavage for genome integrity not tested
  7. 2001 High

    Discovery that MCM3AP is a GNAT-family acetyltransferase that acetylates chromatin-bound MCM3 and inhibits replication initiation (but not elongation) established a post-translational modification pathway that negatively regulates licensing.

    Evidence In vitro acetyltransferase assay with GNAT-motif mutagenesis; cell-free Xenopus replication reconstitution distinguishing initiation from elongation

    PMID:11258703 PMID:12226073

    Open questions at the time
    • Acetylation sites on MCM3 not mapped
    • Deacetylase reversing this modification not identified
    • In vivo physiological trigger for acetylation not defined
  8. 2002 High

    Genetic dissection of two mcm3 alleles separating MCM5 interaction/origin recruitment (Mcm3-10) from post-recruitment initiation (Mcm3-1), combined with discovery that ubiquitination regulates MCM complex assembly, resolved MCM3's role into at least two mechanistically distinct steps during pre-RC formation.

    Evidence Co-IP and ChIP at origins for mcm3-10 and mcm3-1; ubiquitination assays and uba1-165 genetic suppression in S. cerevisiae

    PMID:12060653 PMID:12200430

    Open questions at the time
    • E3 ligase for yeast Mcm3 ubiquitination not identified
    • Relationship between ubiquitination and phosphorylation in complex assembly not tested
  9. 2007 High

    Identification of ATM-mediated phosphorylation of MCM3 at Ser-725/Ser-732, which redistributes MCM3 from chromatin to nucleoplasm, established a direct link between the DNA damage response and MCM complex chromatin dynamics.

    Evidence In vitro ATM kinase assay, phosphospecific antibodies, subcellular fractionation after DNA damage treatment

    PMID:17244605

    Open questions at the time
    • Functional consequence for fork stability or origin firing not directly tested
    • Relationship to checkpoint-mediated replication inhibition not fully resolved
  10. 2008 High

    Mapping CDK1 phosphorylation of MCM3 at Ser-112 as a trigger for MCM2-7 complex assembly and chromatin loading identified a positive regulatory phosphorylation event at the earliest step of pre-RC formation.

    Evidence In vitro CDK1 kinase assay, Ser112Ala phosphomutant, chromatin fractionation, MCM3 knockdown destabilizing other subunits

    PMID:18524952

    Open questions at the time
    • Whether CDK1-S112 phosphorylation is the rate-limiting step for complex formation not tested
    • Temporal relationship to other S112 kinases (PLK1) not resolved
  11. 2011 High

    Demonstrating that cyclin E/Cdk2 phosphorylates MCM3 at Thr-722 for chromatin loading and that this event triggers S-phase checkpoint signaling (CHK1, CDK2 phosphorylation) established MCM3 as both a target and mediator of replication checkpoint control.

    Evidence In vitro cyclin E/Cdk2 kinase assay, T722A phosphomutant chromatin fractionation, flow cytometry and checkpoint marker analysis

    PMID:21965652

    Open questions at the time
    • How T722 phosphorylation is sensed by checkpoint machinery not mechanistically explained
    • Interplay between S112 and T722 phosphorylation events not dissected
  12. 2013 High

    Reconstitution of MCM2-7 helicase with Mcm3-K499A (PS1 hairpin mutant) showing severely impaired DNA unwinding but intact ATPase activity established that MCM3's PS1 hairpin is uniquely essential for translating ATP hydrolysis into strand separation.

    Evidence In vitro reconstituted MCM2-7 helicase assay with individual PS1 mutants across all six subunits, ATPase assays, yeast viability tests

    PMID:24349215

    Open questions at the time
    • Structural basis for why MCM3 PS1 hairpin is uniquely important among six subunits not resolved
    • Whether the defect is in DNA engagement or translocation not distinguished
  13. 2015 High

    Discovery that Chk1 phosphorylates MCM3 at Ser-205 under unperturbed conditions to limit replication fork speed established a constitutive brake on replication that is relieved during replicative stress.

    Evidence In vitro Chk1 kinase assay, S205A mutant DNA fiber analysis showing increased track length and shortened S phase

    PMID:25809478

    Open questions at the time
    • Mechanism by which S205 phosphorylation slows fork progression not defined
    • Whether this affects helicase activity directly or origin firing frequency not resolved
  14. 2016 High

    Identification of the KEAP1-CUL3-RBX1 E3 ligase as the ubiquitylation machinery for chromatin-bound MCM3 — without affecting total protein stability — suggested ubiquitylation modulates MCM complex dynamics on chromatin rather than MCM3 turnover.

    Evidence Substrate-trapping proteomics, in vitro ubiquitylation reconstitution, ubiquitin-remnant profiling, cell cycle-resolved chromatin fractionation

    PMID:27621311

    Open questions at the time
    • Functional consequence of KEAP1-mediated MCM3 ubiquitylation for replication not directly tested
    • Whether ubiquitylation affects helicase activity, origin firing, or fork stability unknown
  15. 2018 Medium

    Demonstration that MCM3 competes with NRF2 for KEAP1 binding via a structural mimic of NRF2's KEAP1-binding motif, and that Pin1 coordinates phosphorylation-dependent MCM3 chromatin dynamics via S112 and T722, integrated MCM3 into both the antioxidant response and cell cycle phosphorylation signaling networks.

    Evidence Biochemical competition binding assays and structural conservation analysis for KEAP1; phosphosite mutagenesis and chromatin fractionation for Pin1

    PMID:29261034 PMID:30108253 PMID:30316783

    Open questions at the time
    • In vivo physiological significance of MCM3-NRF2 competition not demonstrated in non-cancer context
    • Pin1 interaction validated in single lab
    • Negative autoregulatory peptide (MCM3-C) mechanism not resolved structurally
  16. 2024 Medium

    Discovery that USP1 deubiquitinates K48-linked ubiquitin from MCM3, stabilizing it to compete with NRF2 for KEAP1 and thereby activate NRF2-dependent mitophagy in hepatocellular carcinoma, placed MCM3 as an active signaling node beyond its replicative function.

    Evidence Co-IP, deubiquitination assay, MCM3 knockdown, xenograft tumor model

    PMID:41797940

    Open questions at the time
    • Whether USP1-MCM3 axis operates in non-cancer contexts unknown
    • Relationship between replicative and NRF2-modulatory functions of MCM3 not integrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for why MCM3's PS1 hairpin is uniquely essential among MCM subunits for unwinding; how the multiple phosphorylation inputs (CDK1, Cdk2, Chk1, ATM, PLK1) are temporally coordinated on a single MCM3 molecule; and whether MCM3's non-replicative role in KEAP1-NRF2 signaling represents a physiological function or a pathological co-option.
  • No integrated temporal phosphorylation map of MCM3 in a single system
  • Structural mechanism of PS1 hairpin in unwinding not resolved
  • MCM3-KEAP1-NRF2 axis not tested in normal physiology

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0140657 ATP-dependent activity 1
Localization
GO:0005694 chromosome 7 GO:0005634 nucleus 4 GO:0005654 nucleoplasm 2
Pathway
R-HSA-69306 DNA Replication 7 R-HSA-1640170 Cell Cycle 6 R-HSA-73894 DNA Repair 2 R-HSA-5357801 Programmed Cell Death 1
Partners
GANPKEAP1MCM3APMCM5PIN1USP1
Complex memberships
KEAP1-CUL3-RBX1 E3 ligase (substrate)MCM2-7 hexamer

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Xenopus MCM3 (XMCM3) is a component of the replication licensing factor; it binds sperm DNA before nuclear formation, is required for DNA replication, and dissociates from nuclear DNA during replication progression without being transported into nuclei, establishing its role in restricting re-replication. Immunodepletion of Xenopus egg extracts, replication assays with sperm/HeLa nuclei templates, cDNA cloning and sequencing Cell High 7758114 7760938
1993 Yeast MCM2 and MCM3 proteins undergo cell cycle-regulated nuclear localization: they enter the nucleus at the end of mitosis, persist through G1, disappear at the start of S phase, and a fraction becomes tightly chromatin-associated, establishing their role in ensuring DNA replication occurs once per cell cycle. Two-dimensional gel electrophoresis, cell cycle fractionation, subnuclear localization studies in Saccharomyces cerevisiae Genes & Development High 8224843
1991 Yeast Mcm2 and Mcm3 are genetically interacting essential proteins with overlapping roles in DNA replication initiation; double mutants are inviable and overproduction of one affects the phenotype of the other, indicating they function in complementary or interacting roles. Genetic epistasis, double-mutant analysis, overexpression complementation assays in Saccharomyces cerevisiae Genes & Development High 2044961
1994 Murine MCM3 (P1 protein) exists in underphosphorylated (chromatin-associated) and hyperphosphorylated (loosely nuclear-bound) forms; during S phase progression, the underphosphorylated form dissociates from nuclear structure in parallel with temporally ordered DNA replication, consistent with cell cycle-dependent phosphorylation regulating its chromatin release. Polyclonal antibody staining, fractionation, cell-cycle synchronization, immunofluorescence of mouse cell line The EMBO Journal High 7925275
1995 The nuclear envelope prevents binding of XMCM3 to chromatin (not nuclear entry per se); chromatin binding requires a cytosolic 'loading factor' that is excluded by the nuclear membrane, resolving licensing into two stages: loading factor entry and subsequent MCM3 chromatin binding. Nuclear envelope permeabilization, immunofluorescence, Xenopus egg extract replication assays Current Biology High 8574584
1992 Human MCM3 (P1 protein) is specifically localized to the nucleus and physically associates with complex forms of DNA polymerase alpha-primase in cell extracts. Immunoprecipitation/co-purification with DNA polymerase alpha-primase, nuclear fractionation, cDNA cloning Nucleic Acids Research Medium 1549468
1995 Mouse MCM3 (P1) physically interacts with CDC46 (MCM5) protein, establishing that MCM proteins function coordinately as a complex for DNA replication. Immunochemical co-precipitation (reciprocal pulldown), cDNA cloning Nucleic Acids Research Medium 7610039
2001 MCM3AP (MCM3-associated protein) is an acetyltransferase that directly acetylates MCM3; chromatin-bound MCM3 is acetylated in vivo; MCM3AP contains GCN5-related N-acetyltransferase (GNAT) motifs essential for activity; overexpression of MCM3AP inhibits DNA replication, and mutation of acetyltransferase motifs abolishes this inhibitory effect. Yeast two-hybrid screen, in vitro acetyltransferase assay, site-directed mutagenesis of GNAT motifs, overexpression replication assays EMBO Reports High 11258703
2002 MCM3AP inhibits the initiation but not elongation of DNA replication via its acetyltransferase activity; MCM3AP binds chromatin through interaction with MCM3 and requires this interaction for its nuclear localization; chromatin binding of MCM3AP is temporally correlated with endogenous MCM3 chromatin association. Cell-free Xenopus replication system, wild-type vs. acetyltransferase-deficient mutant MCM3AP, chromatin binding assays The Journal of Biological Chemistry High 12226073
1998 Map80 (MCM3-associated protein, 80 kDa) binds MCM3 and facilitates its nuclear localization; mutation of the MCM3 nuclear localization signal disrupts Map80 binding; addition of recombinant Map80 increases nuclear-localized MCM3. Yeast two-hybrid screen, immunoprecipitation, NLS mutagenesis, recombinant protein addition assays The Journal of Biological Chemistry Medium 9712829
2008 CDK1 phosphorylates MCM3 at Ser-112 (and also Ser-611 and Thr-719); phosphorylation of Ser-112 by CDK1 in vivo triggers MCM3 assembly with other MCM subunits and subsequent chromatin loading of the MCM2-7 complex; loss of MCM3 destabilizes other MCM proteins. CDK1 kinase assays, phosphomutant (Ser112Ala) overexpression, chromatin fractionation, MCM3 knockdown Proceedings of the National Academy of Sciences USA High 18524952
2011 Cyclin E/Cdk2 phosphorylates MCM3 at Thr-722; MCM3 T722A mutant shows severely reduced chromatin binding compared to wild-type; overexpression of wild-type but not T722A MCM3 inhibits S phase entry and upregulates CHK1 Ser-345 and CDK2 Thr-14 phosphorylation, implicating this phosphorylation in S phase checkpoint control. In vitro kinase assay (cyclin E/Cdk2), phosphomutant expression, chromatin fractionation, flow cytometry, Western blot The Journal of Biological Chemistry High 21965652
2007 ATM phosphorylates MCM3 at Ser-725 and Ser-732 in its C-terminus in vitro and in vivo; ATM-phosphorylated MCM3 is preferentially localized to the soluble nucleoplasmic fraction rather than chromatin; ATM and ATR jointly contribute to UV-induced MCM3 phosphorylation. Phosphospecific antibody purification, in vitro ATM kinase assay, subcellular fractionation, DNA damage treatment The Journal of Biological Chemistry High 17244605
2015 Chk1 phosphorylates MCM3 at Ser-205 under normal growth conditions; Ser205Ala mutation increases DNA replication track length and shortens S phase, indicating that this phosphorylation negatively regulates normal DNA replication; upon replicative stress, reduction of this phosphorylation correlates with ssDNA generation and ATR activation. In vitro Chk1 kinase assay, phosphomutant (S205A) expression, DNA fiber assay, flow cytometry The Journal of Biological Chemistry High 25809478
1998 MCM3, but not other MCM family members, is selectively cleaved early during apoptosis; this cleavage is prevented by caspase inhibitors and does not occur during necrosis, identifying MCM3 as a caspase substrate that inactivates the MCM complex during cell death. Multiple apoptosis models, caspase inhibitor treatment, Western blot, comparison with necrosis Experimental Cell Research Medium 9473350
2016 KEAP1 ubiquitylates MCM3 via the KEAP1-CUL3-RBX1 E3 ligase complex; KEAP1 does not regulate total MCM3 protein stability or subcellular localization but associates with chromatin in a cell cycle-dependent manner parallel to MCM2-7, suggesting it modulates MCM complex dynamics; specific KEAP1-dependent ubiquitylation sites on predicted exposed surfaces of the MCM2-7 complex were identified. Substrate-trapping proteomics, in vitro ubiquitylation assay, ubiquitin remnant profiling, chromatin fractionation The Journal of Biological Chemistry High 27621311
2018 MCM3 competes with NRF2 for KEAP1 binding via a conserved motif structurally mimicking NRF2's KEAP1-binding domain (helix-2-insert motif of MCM3); this competition modulates KEAP1-controlled NRF2 antioxidant response activity. Biochemical binding assays, structural analysis, competition binding experiments, sequence/structural conservation analysis Scientific Reports Medium 30108253
2002 Yeast Mcm3 is polyubiquitinated at the onset of MCM complex assembly (during mitosis); reducing ubiquitination rate (via uba1-165 mutation) restores MCM3-10 interaction with MCM subunits and its recruitment to replication origins, suggesting ubiquitination regulates MCM complex assembly. Ubiquitination assay in S. cerevisiae, genetic suppressor analysis (uba1-165 suppressor of mcm3-10), chromatin immunoprecipitation The Journal of Biological Chemistry Medium 12200430
2002 Two yeast mcm3 mutations are defective at distinct steps of replication initiation: Mcm3-10 (P118L) compromises interaction with Mcm5 and prevents recruitment of the MCM2-7 complex to replication origins; Mcm3-1 (G246E) diminishes replication initiation efficiency without affecting MCM5 interaction or origin recruitment. Genetic characterization, co-immunoprecipitation, chromatin immunoprecipitation for origin association The Journal of Biological Chemistry High 12060653
2013 The pre-sensor 1 (PS1) hairpin lysine of MCM3 (K499) is essential for viability in yeast; MCM2-7 complex reconstituted with Mcm3-K499A shows severely decreased helicase activity without proportional loss of ATPase activity, indicating the PS1 hairpin of MCM3 is specifically required for DNA unwinding. Site-directed mutagenesis of PS1 hairpin in each MCM subunit, in vitro helicase and ATPase reconstitution assays, EMSA PLoS One High 24349215
1997 MCM3 nuclear accumulation in S. cerevisiae requires a specific nuclear localization sequence (NLS); the NLS is necessary for nuclear import and sufficient to direct beta-galactosidase to the nucleus; cell cycle-specific nuclear accumulation of Mcm3 is due to nuclear retention rather than regulated NLS-based import. NLS mutagenesis, NLS fusion with beta-galactosidase reporter, cell cycle analysis Genes to Cells Medium 9427284
2025 In S. cerevisiae Mcm3, precise positioning of basic residues within the NLS is critical for nuclear import via importin interactions; disruption of these interactions impairs nuclear import of Mcm3 and chromatin loading of the MCM complex, resulting in poor cell growth; AlphaFold 3 modeling supports the interaction mechanism. Mutagenesis of NLS basic residues, AlphaFold 3 structural modeling, chromatin fractionation, cell growth assays PLoS Genetics Medium 39836669
2018 MCM3 interacts with Pin1 prolyl isomerase via its WW domain; Pin1 interaction requires proline-directed phosphorylation of MCM3 at S112 and T722; Pin1 coordinates phosphorylation-dependent MCM3 loading onto and unloading from chromatin, mediating S phase control. Binding assays, mutagenesis of S112 and T722 phosphosites, chromatin fractionation Journal of Molecular Biology Medium 30316783
2019 PLK1 phosphorylates MCM3 at Ser-112 in a PLK1-dependent manner; PLK1-mediated MCM3 phosphorylation promotes cell cycle progression and suppresses apoptosis in renal cell carcinoma cells in vitro and promotes tumor growth in vivo. Mn2+-Phos-tag SDS-PAGE, Western blot, immunofluorescence, PLK1 overexpression/knockout, xenograft mouse model Cancer Gene Therapy Medium 31186514
2000 GANP protein associates with MCM3 in B cells; GANP has a domain (Map-box) capable of binding MCM3 and carries DNA primase activity, suggesting GANP modulates MCM3-dependent DNA replication in germinal center B cells. Co-immunoprecipitation, nuclear protein characterization, expression correlation in B cells Blood Low 10733502
2002 G5PR (a phosphatase regulatory subunit homolog) associates with the GANP/MCM3 complex and recruits PP5 and PP2A phosphatases that can dephosphorylate MCM3 in vitro, suggesting a phosphatase complex regulates MCM3 phosphorylation state during cell cycle progression. Yeast two-hybrid, pulldown assays, in vitro phosphatase activity assay on MCM3 Genes to Cells Low 12167160
2018 MCM3 loaded onto DNA in Xenopus egg extracts prevents binding of loading factors ORC, Cdc6, and Cdt1 to nearby DNA; a peptide from the C-terminal region of MCM3 (MCM3-C) mimics this inhibitory activity, suggesting a negative autoregulatory mechanism that interferes with MCM loading near licensed origins. Cell-free Xenopus egg extract MCM loading assay, MCM3-C peptide competition assay, ATP-γ-S inhibition Cell Cycle Medium 29261034
2025 Cryo-EM analysis of human MCM2-7 reveals that the MCM3 winged helix domain (WHD) docks on MCM2 in both DNA-free double hexamer and single hexamer, creating a 'safety latch' across the DNA entry gate to block DNA entry; this latch is opened by ORC-CDC6 binding; disease-related or designed mutations disrupting this latch cause replication defects and DNA damage checkpoint activation. Cryo-EM structure of DNA-free human MCM2-7, site-directed mutagenesis, functional replication assays, checkpoint activation assays bioRxivpreprint High
1997 Yeast Mcm3 is a phosphoprotein with multiple isoforms; distinct phosphorylated isoforms appear at specific cell cycle stages; only a small fraction of total cellular Mcm3 tightly associates with chromatin from late M through beginning of S phase, while the remainder is distributed in cytoplasm and nucleoplasm. 2D protein gel analysis, cell cycle synchronization, chromatin fractionation in S. cerevisiae Molecular Biology of the Cell Medium 9285827
2010 Human cytomegalovirus IE86 protein binds to cellular MCM3 but does not inhibit MCM3 binding to the EBV replication origin (oriP) in U373MG cells, indicating the IE86-MCM3 interaction alone is not sufficient to block MCM3's origin association in this cell type. Co-immunoprecipitation, chromatin immunoprecipitation at EBV oriP Acta Virologica Low 20545442
2024 USP1 binds to MCM3 and stabilizes it by removing K48-linked ubiquitin chains (deubiquitination); stabilized MCM3 binds to KEAP1, disrupting the KEAP1-NRF2 interaction and thereby activating NRF2 signaling to modulate mitophagy and promote HCC progression. Co-immunoprecipitation, deubiquitination assay, MCM3 knockdown, in vivo xenograft model iScience Medium 41797940

Source papers

Stage 0 corpus · 85 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Identification of the yeast MCM3-related protein as a component of Xenopus DNA replication licensing factor. Cell 257 7758114
1995 MCM3 complex required for cell cycle regulation of DNA replication in vertebrate cells. Nature 253 7760938
1993 Cell cycle-regulated nuclear localization of MCM2 and MCM3, which are required for the initiation of DNA synthesis at chromosomal replication origins in yeast. Genes & development 210 8224843
1991 Mcm2 and Mcm3, two proteins important for ARS activity, are related in structure and function. Genes & development 184 2044961
1994 DNA polymerase alpha associated protein P1, a murine homolog of yeast MCM3, changes its intranuclear distribution during the DNA synthetic period. The EMBO journal 159 7925275
1992 Properties of the nuclear P1 protein, a mammalian homologue of the yeast Mcm3 replication protein. Nucleic acids research 124 1549468
1990 The phenotype of the minichromosome maintenance mutant mcm3 is characteristic of mutants defective in DNA replication. Molecular and cellular biology 117 2233713
1995 The nuclear envelope prevents reinitiation of replication by regulating the binding of MCM3 to chromatin in Xenopus egg extracts. Current biology : CB 109 8574584
2001 MCM3AP, a novel acetyltransferase that acetylates replication protein MCM3. EMBO reports 76 11258703
2016 Identification and Characterization of MCM3 as a Kelch-like ECH-associated Protein 1 (KEAP1) Substrate. The Journal of biological chemistry 74 27621311
1998 Stability of the replicative Mcm3 protein in proliferating and differentiating human cells. Experimental cell research 73 9633535
1995 Molecular cloning of cDNA encoding mouse Cdc21 and CDC46 homologs and characterization of the products: physical interaction between P1(MCM3) and CDC46 proteins. Nucleic acids research 72 7610039
1997 Mcm2 and Mcm3 are constitutive nuclear proteins that exhibit distinct isoforms and bind chromatin during specific cell cycle stages of Saccharomyces cerevisiae. Molecular biology of the cell 71 9285827
2002 Two E2F sites in the Arabidopsis MCM3 promoter have different roles in cell cycle activation and meristematic expression. The Journal of biological chemistry 67 12089153
2001 The expression of Ki-67, MCM3, and p27 defines distinct subsets of proliferating, resting, and differentiated cells. The Journal of pathology 64 11745678
2000 A novel nuclear phosphoprotein, GANP, is up-regulated in centrocytes of the germinal center and associated with MCM3, a protein essential for DNA replication. Blood 55 10733502
2008 Phosphorylation of MCM3 on Ser-112 regulates its incorporation into the MCM2-7 complex. Proceedings of the National Academy of Sciences of the United States of America 44 18524952
2019 PLK1 promotes proliferation and suppresses apoptosis of renal cell carcinoma cells by phosphorylating MCM3. Cancer gene therapy 41 31186514
2013 MCM3 as a novel diagnostic marker in benign and malignant salivary gland tumors. Asian Pacific journal of cancer prevention : APJCP 40 23886132
1998 Selective proteolysis of the nuclear replication factor MCM3 in apoptosis. Experimental cell research 40 9473350
2011 Phosphorylation of MCM3 protein by cyclin E/cyclin-dependent kinase 2 (Cdk2) regulates its function in cell cycle. The Journal of biological chemistry 39 21965652
1995 Cdc54 belongs to the Cdc46/Mcm3 family of proteins which are essential for initiation of eukaryotic DNA replication. Gene 38 7698653
2000 Structure, expression, and chromosomal localization of the human gene encoding a germinal center-associated nuclear protein (GANP) that associates with MCM3 involved in the initiation of DNA replication. Gene 37 11024281
2002 The MCM3 acetylase MCM3AP inhibits initiation, but not elongation, of DNA replication via interaction with MCM3. The Journal of biological chemistry 36 12226073
2007 Identification of carboxyl-terminal MCM3 phosphorylation sites using polyreactive phosphospecific antibodies. The Journal of biological chemistry 35 17244605
2015 Immunoexpression of Ki-67, MCM2, and MCM3 in Ameloblastoma and Ameloblastic Carcinoma and Their Correlations with Clinical and Histopathological Patterns. Disease markers 31 26823641
2015 Phosphorylation of Minichromosome Maintenance 3 (MCM3) by Checkpoint Kinase 1 (Chk1) Negatively Regulates DNA Replication and Checkpoint Activation. The Journal of biological chemistry 30 25809478
1998 Identification of a novel MCM3-associated protein that facilitates MCM3 nuclear localization. The Journal of biological chemistry 30 9712829
2023 Pyrroloquinoline quinone alleviates natural aging-related osteoporosis via a novel MCM3-Keap1-Nrf2 axis-mediated stress response and Fbn1 upregulation. Aging cell 29 37365714
2002 MCM3-binding GANP DNA-primase is associated with a novel phosphatase component G5PR. Genes to cells : devoted to molecular & cellular mechanisms 27 12167160
2018 MCM3: A Novel Proliferation Marker in Oral Squamous Cell Carcinoma. Applied immunohistochemistry & molecular morphology : AIMM 26 27258565
2018 Keap1-MCM3 interaction is a potential coordinator of molecular machineries of antioxidant response and genomic DNA replication in metazoa. Scientific reports 25 30108253
1997 Nuclear accumulation of Saccharomyces cerevisiae Mcm3 is dependent on its nuclear localization sequence. Genes to cells : devoted to molecular & cellular mechanisms 25 9427284
2023 m6A demethylase FTO stabilizes LINK-A to exert oncogenic roles via MCM3-mediated cell-cycle progression and HIF-1α activation. Cell reports 23 37858471
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
2014 MCM3 could be a better marker than Ki-67 for evaluation of dysplastic oral lesions: an immunohistochemical study. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 22 24456424
2003 Expression of replication-licensing factors MCM2 and MCM3 in normal, hyperplastic, and carcinomatous endometrium: correlation with expression of Ki-67 and estrogen and progesterone receptors. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 22 14501812
2015 Expression of MCM-3 and MCM-7 in Primary Cutaneous T-cell Lymphomas. Anticancer research 21 26504025
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
2010 Increase of Mcm3 and Mcm4 expression in cervical squamous cell carcinomas. European journal of gynaecological oncology 19 21077471
2021 MCM3 upregulation confers endocrine resistance in breast cancer and is a predictive marker of diminished tamoxifen benefit. NPJ breast cancer 17 33398005
2021 MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma. Virchows Archiv : an international journal of pathology 17 34782936
2003 Genes encoding two essential DNA replication activation proteins, Cdc6 and Mcm3, exhibit very different patterns of expression in the tobacco BY-2 cell cycle. Journal of experimental botany 17 12554713
1999 Involvement of cyclin D1-cdk5 overexpression and MCM3 cleavage in bax-associated spontaneous apoptosis and differentiation in an A253 human head and neck carcinoma xenograft model. International journal of cancer 16 10495426
2015 Evaluation of Minichromosome Maintenance-3 (MCM3) in Oral Squamous Cell Carcinoma. Journal of dentistry (Shiraz, Iran) 14 26046103
2018 MCM3 and Ki67 proliferation markers in odontogenic cysts and ameloblastoma. Journal of oral biology and craniofacial research 13 30225187
2013 The PS1 hairpin of Mcm3 is essential for viability and for DNA unwinding in vitro. PloS one 12 24349215
1998 cDNA cloning and expression during development of Drosophila melanogaster MCM3, MCM6 and MCM7. Gene 12 9795205
2017 Evaluation of the Ki-67 and MCM3 Expression in Cytologic Smear of Oral Squamous Cell Carcinoma. Journal of dentistry (Shiraz, Iran) 11 29034276
2015 Arabidopsis thaliana MCM3 single subunit of MCM2-7 complex functions as 3' to 5' DNA helicase. Protoplasma 11 25944245
2002 Two mcm3 mutations affect different steps in the initiation of DNA replication. The Journal of biological chemistry 11 12060653
2002 Mcm3 is polyubiquitinated during mitosis before establishment of the pre-replication complex. The Journal of biological chemistry 11 12200430
2024 LncRNA GAS6-AS1 contributes to 5-fluorouracil resistance in colorectal cancer by facilitating the binding of PCBP1 with MCM3. Cancer letters 10 38521199
2021 Irisin Association with Ki-67, MCM3 and MT-I/II in Squamous Cell Carcinomas of the Larynx. Biomolecules 10 35053200
2016 Up-regulation of MCM3 Relates to Neuronal Apoptosis After Traumatic Brain Injury in Adult Rats. Cellular and molecular neurobiology 9 27401074
2014 Evolutionary diversification of MCM3 genes in Xenopus laevis and Danio rerio. Cell cycle (Georgetown, Tex.) 9 25485507
2017 Expression of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and topoisomerase IIα) in borderline ovarian tumors: Correlation with clinicopathological features. Histology and histopathology 8 28493257
2013 In vitro study on the effect of doxorubicin on the proliferation markers MCM3 and Ki-67. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 8 24344040
2018 CDK phosphorylation regulates Mcm3 degradation in budding yeast. Biochemical and biophysical research communications 5 30376991
2016 Mcm3 replicative helicase mutation impairs neuroblast proliferation and memory in Drosophila. Genes, brain, and behavior 5 27283469
2000 Genomic structure of the gene for the human P1 protein (MCM3) and its exclusion as a candidate for autosomal recessive polycystic kidney disease. European journal of human genetics : EJHG 5 10780780
2023 Rac GTPase activating protein 1 promotes the glioma growth by regulating the expression of MCM3. Translational oncology 4 37595394
2022 Systematic analysis of MCM3 in pediatric medulloblastoma via multi-omics analysis. Frontiers in molecular biosciences 4 36133906
2021 MCM3 proliferative index is worthier over Ki-67 in the characterization of salivary gland tumors. Indian journal of pathology & microbiology 4 33433405
2021 The Immunohistochemical Expression of MCM-3, -5, and -7 Proteins in the Uterine Fibroids. Current issues in molecular biology 4 34449552
2018 MCM interference during licensing of DNA replication in Xenopus egg extracts-Possible Role of a C-terminal region of MCM3. Cell cycle (Georgetown, Tex.) 4 29261034
2025 Gobal crotonylome reveals that HNRNPC and its crotonylation promote p53-deficient tumor growth by stabilizing CCND1 and MCM3 mRNAs. Cancer letters 3 40482911
2024 A novel upregulated hsa_circ_0032746 regulates the oncogenesis of esophageal squamous cell carcinoma by regulating miR-4270/MCM3 axis. Human genomics 3 38200573
2024 Expression, potential biological behaviour and clinical significance of MCM3 in pancreatic adenocarcinoma: a comprehensive study integrating high throughput sequencing, CRISPR screening and in-house immunohistochemistry. Annals of medicine 3 39310930
2023 Quantitative Proteomic Analysis of MCM3 in ThinPrep Samples of Patients with Cervical Preinvasive Cancer. International journal of molecular sciences 3 37445651
2022 Corrigendum: Systematic analysis of MCM3 in pediatric medulloblastoma via multi-omics analysis. Frontiers in molecular biosciences 3 36452454
2016 Comparison between immunohistochemical expression of Ki-67 and MCM-3 in major salivary gland epithelial tumors in children and adolescents. Preliminary study. Polish journal of pathology : official journal of the Polish Society of Pathologists 3 28547962
2025 MCM3 promotes hepatocellular carcinoma progression via Epithelial-mesenchymal Transition through AKT/Twist signaling pathway. Annals of hepatology 2 39978465
2018 Regulation of the Minichromosome Maintenance Protein 3 (MCM3) Chromatin Binding by the Prolyl Isomerase Pin1. Journal of molecular biology 2 30316783
2017 [Deguelin inhibits proliferation and regulates the expression of MCM3-CDC45 in MCF-7 and H1299 cells in vitro]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 2 29180339
2010 Human cytomegalovirus IE86 protein binds to cellular Mcm3 protein but does not inhibit its binding to the Epstein-Barr virus oriP in U373MG-p220.2 cells. Acta virologica 2 20545442
2023 Immunohistochemical Comparison of Ki-67 and MCM-3 in Odontogenic Cysts: An Observational Study. Applied immunohistochemistry & molecular morphology : AIMM 1 38062794
2023 Expression analysis of cyclin D, Ki-67, MCM3 and MCM2 in oral squamous cell carcinoma. Bioinformation 1 38415027
2021 Downregulation of circular RNA circDOCK7 identified from diabetic rats after sleeve gastrectomy contributes to hepatocyte apoptosis through regulating miR-139-3p and MCM3. Biochemical and biophysical research communications 1 33640606
2026 A cancer-specific pipeline uncovers MCM3 as a driver of glioblastoma progression via suppression of the Wnt pathway. International journal of biological macromolecules 0 41638282
2026 USP1 promotes hepatocellular carcinoma progression by modulating mitophagy via stabilizing MCM3 to regulate the Keap1-Nrf2 axis. iScience 0 41797940
2025 Sequence specificity of an essential nuclear localization sequence in Mcm3. PLoS genetics 0 39836669
2025 ZMIZ2/MCM3 Axis Participates in Triple-Negative Breast Cancer Progression. Oncology research 0 41502508
2024 Sequence specificity of an essential nuclear localization sequence in Mcm3. bioRxiv : the preprint server for biology 0 39605614
2021 Identification of mungbean yellow mosaic India virus (MYMIV) Rep interacting partners using phage display and influence of Arabidopsis thaliana MCM3 on geminivirus DNA replication. Journal of biomolecular structure & dynamics 0 34121621