Affinage

MCM5

DNA replication licensing factor MCM5 · UniProt P33992

Length
734 aa
Mass
82.3 kDa
Annotated
2026-06-10
71 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MCM5 (CDC46/nda4) is a core subunit of the eukaryotic MCM2-7 replicative helicase required for initiation of DNA replication at the G1/S transition, established by genetic studies in budding and fission yeast where loss arrests cells with unreplicated DNA (PMID:1438234, PMID:8298187). Within the heterohexamer, the Mcm2/Mcm5 ATPase active site forms a regulatory gate controlling DNA entry into the helicase ring, with the adjacent MCM5/3 site modulating gate activity (PMID:17895243, PMID:20484375), and the Mcm5 C-terminus reads out ring closure by contacting Orc3 in the ORC-Cdc6-Cdt1-MCM2-7 loading intermediate, triggering Mcm4 ATP hydrolysis that remodels the pre-RC and releases Cdt1 (PMID:39747125). Mcm5 conformation imposes a block to origin firing that is relieved by Cdc7-Dbf4 (DDK) kinase, a control circumvented by the mcm5-bob1/P83L mutation (PMID:9096361, PMID:17724082), and UFL1-catalyzed UFMylation of MCM5 at Lys583 stabilizes the CMG helicase for efficient origin firing and fork progression (PMID:40940420). Replication loading is governed by Cdc6, which controls both Mcm5 deposition on and removal from origins (PMID:10945234). Beyond replication, MCM5 has a direct transcriptional role: it binds the Stat1 transactivation domain in a Ser727-phosphorylation-dependent manner through residues R732/K734, recruiting an MCM5/MCM3 subcomplex to cytokine-responsive promoters and traveling with elongating RNA polymerase II to activate Stat1 target genes (PMID:9843502, PMID:11248027, PMID:16199513). MCM5 also restrains centrosome reduplication by binding cyclins E and A at centrosomes through a conserved CLS-dependent domain independent of its MCM partners (PMID:18799789, PMID:20663915). Biallelic MCM5 mutations cause Meier-Gorlin syndrome, and defects in MCM5 UFMylation are linked to microcephalic primordial dwarfism (PMID:28198391, PMID:40940420).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1992 High

    Establishing that CDC46 and MCM5 are the same essential gene defined MCM5 as a factor required specifically for initiation of DNA replication, framing all later mechanistic work.

    Evidence Complementation, genetic linkage, minichromosome maintenance and DNA content analysis in S. cerevisiae

    PMID:1438234

    Open questions at the time
    • Does not define molecular activity within the helicase
    • No biochemical reconstitution of MCM5 function
  2. 1990 High

    Cell-cycle-regulated nuclear localization of CDC46/MCM5 answered how replication factor availability is restricted to once per cycle.

    Evidence Cell fractionation and immunolocalization across the cell cycle in S. cerevisiae

    PMID:2279699

    Open questions at the time
    • Mechanism of import/export not identified
    • Does not address activity of MCM5 on chromatin
  3. 1996 Medium

    Demonstrating that nuclear MCM5 forms a stable complex with MCM3 in mammalian cells established MCM5 as a constitutive partner within the MCM family rather than a free monomer.

    Evidence cDNA cloning, immunoprecipitation, and FISH mapping in mouse and human cells

    PMID:7610039 PMID:8751386

    Open questions at the time
    • Single Co-IP without reciprocal mapping of interface
    • Does not define the full MCM2-7 hexamer architecture
  4. 1997 High

    The mcm5-bob1 suppressor revealed that Mcm5 itself imposes a block to origin firing that DDK kinase relieves, placing MCM5 at the heart of replication-initiation control.

    Evidence Genetic suppressor screen and epistasis with cdc7/dbf4 in S. cerevisiae

    PMID:9096361

    Open questions at the time
    • Conformational basis of the block not yet resolved
    • DDK phosphosite on MCM5 not mapped
  5. 1998 High

    Discovery that MCM5 binds the Stat1 transactivation domain in a Ser727-dependent manner identified an unexpected replication-independent transcriptional function.

    Evidence In vitro binding, Co-IP, reporter assays, and mass spectrometry

    PMID:9843502

    Open questions at the time
    • Mechanism of transcriptional enhancement at promoters not yet defined
    • MCM5 residues mediating Stat1 binding not yet mapped
  6. 1999 High

    Identifying MCM5 as an E2F target gene connected its expression to growth and cell-cycle entry.

    Evidence Promoter-reporter assays with E2F site mutations and forced E2F1 expression

    PMID:10327050

    Open questions at the time
    • Does not address protein-level regulation
    • Other transcriptional inputs not examined
  7. 2001 High

    Mapping MCM5 residues R732/K734 to the Stat1 interaction and showing MCM3 co-purifies via MCM5 established that Stat1 recruits a defined MCM5/MCM3 subcomplex for transcription.

    Evidence Site-directed mutagenesis, in vitro binding, Co-IP, gel filtration, reporter assays

    PMID:11248027

    Open questions at the time
    • Whether ATPase/helicase activity is mechanistically required at promoters unresolved
    • Composition of promoter-bound MCM complex incomplete
  8. 2005 High

    Showing MCM5 is inducibly recruited to Stat1 promoters and travels with elongating Pol II, and is required for target-gene transcription, cemented its direct transcriptional role.

    Evidence ChIP, RNAi knockdown, dominant-negative domain overexpression, reporter assays

    PMID:16199513

    Open questions at the time
    • Step in transcription cycle that MCM5 acts on not defined
    • Relationship to replicative MCM2-7 pool unclear
  9. 2000 Medium

    Demonstrating that Cdc6 controls both loading and unloading of Mcm5 on origins clarified how MCM5 chromatin association is restricted to prevent re-replication.

    Evidence ChIP, chromatin fractionation, and ts-mutant analysis in S. cerevisiae

    PMID:10945234

    Open questions at the time
    • Single lab, specific cdc6 mutant
    • Direct contacts between Cdc6 and Mcm5 not mapped
  10. 2007 High

    Biochemical and genetic work defined the Mcm2/Mcm5 ATPase site as a regulatory DNA gate and the bob1 conformation as the final DDK target controlling firing efficiency.

    Evidence In vitro ATPase/ssDNA-binding assays with purified MCM2-7 and intragenic suppressor genetics with structural modeling

    PMID:17724082 PMID:17895243

    Open questions at the time
    • Atomic structure of the gate not yet available at this stage
    • How DDK phosphorylation alters the gate conformation not directly shown
  11. 2008 High

    Active-site and beta-hairpin mutagenesis established that all six MCM subunits coordinate origin binding and that heterohexameric ATPase sites contribute unequally, with MCM5/3 and MCM6/2 modulating the MCM2/5 gate.

    Evidence Structure-guided mutagenesis, ChIP, synthetic lethality, and reconstituted ATPase/helicase assays

    PMID:18660534 PMID:20484375

    Open questions at the time
    • Mechanistic coupling of gate to translocation not fully resolved
    • In vivo relevance of unequal site contributions not tested
  12. 2008 High

    Identifying a conserved CLS-dependent domain in MCM5 that binds cyclin E (and later cyclin A) at centrosomes revealed a moonlighting role restraining centrosome reduplication.

    Evidence Reciprocal Co-IP, CLS mutagenesis, and centrosome-duplication assays in CHO cells

    PMID:18799789 PMID:20663915

    Open questions at the time
    • Molecular mechanism by which MCM5 inhibits reduplication unknown
    • Whether this operates in normal cycling cells unclear
  13. 2017 High

    Biallelic MCM5 mutations causing Meier-Gorlin syndrome established human disease relevance and confirmed in vivo developmental requirement.

    Evidence Exome sequencing, yeast complementation, patient cell-cycle analysis, and zebrafish knockdown

    PMID:28198391

    Open questions at the time
    • Tissue-specific basis of the growth phenotype not defined
    • Whether disease reflects replication or non-replication functions unclear
  14. 2025 High

    A cryo-EM loading intermediate showed the Mcm5 C-terminus recognizes the closed Mcm2/5 ring via Orc3 contact and triggers Mcm4 ATP hydrolysis to release Cdt1, mechanistically defining how ring closure drives pre-RC remodeling.

    Evidence Cryo-EM, interface mutagenesis, ATPase and helicase-loading assays

    PMID:39747125

    Open questions at the time
    • How DDK phosphorylation integrates with this structural checkpoint not shown
    • Dynamics of subsequent double-hexamer formation not captured
  15. 2025 High

    Identifying UFL1-catalyzed UFMylation of MCM5 at Lys583 linked a post-translational modification to CMG stability, firing efficiency, and fork speed, connecting MCM5 to microcephalic primordial dwarfism.

    Evidence In vitro UFMylation, Lys583 mutagenesis, DNA fiber and origin-firing assays, CMG stability analysis

    PMID:40940420

    Open questions at the time
    • How UFMylation physically stabilizes CMG not structurally resolved
    • Regulation of UFMylation timing during the cycle unknown
  16. 2025 Medium

    A zebrafish/mouse study extended the MCM5-Stat1 axis to T cell survival, showing MCM5 binds Stat1a and promotes its phosphorylation to drive bcl2 expression and protect replication-stressed thymocytes from apoptosis.

    Evidence mcm5 mutant analysis, Co-IP, Stat1 phosphorylation and bcl2 expression assays, mouse validation

    PMID:39929806

    Open questions at the time
    • How MCM5 facilitates Stat1 phosphorylation mechanistically unknown
    • Single-lab Co-IP without interface mapping

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MCM5's distinct activities — replicative helicase loading, Stat1-dependent transcription, centrosome restraint, and modification-dependent CMG stabilization — are partitioned and coordinated within a cell remains unresolved.
  • No structure of MCM5 engaged with Stat1
  • Functional separation of replicative vs. moonlighting pools undefined
  • Regulation linking UFMylation, DDK, and the Mcm2/5 gate not integrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 3 GO:0140657 ATP-dependent activity 3 GO:0003677 DNA binding 2 GO:0098772 molecular function regulator activity 2 GO:0140097 catalytic activity, acting on DNA 2
Localization
GO:0005634 nucleus 2 GO:0005694 chromosome 2 GO:0005815 microtubule organizing center 2
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 3 R-HSA-69306 DNA Replication 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
CCNA2CCNE1HDAC1MCM3ORC3STAT1UFL1
Complex memberships
CMG complexMCM2-7 replicative helicaseMCM5/MCM3 subcomplexORC-Cdc6-Cdt1-MCM2-7 pre-RC intermediate

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 Yeast CDC46/MCM5 protein accumulates in the nucleus of non-dividing interphase cells and rapidly disappears from the nucleus at the G1-S boundary, correlating with DNA replication initiation; the shift in localization is not due to changes in total protein levels, indicating cell cycle-regulated nuclear export/import as a mechanism to restrict DNA replication to once per cycle. Cell fractionation and immunolocalization across cell cycle stages in S. cerevisiae Genes & development High 2279699
1992 CDC46 and MCM5 are identical genes in S. cerevisiae (confirmed by complementation and genetic linkage); cdc46/mcm5 mutants arrest at G1/S with unreplicated DNA and show increased minichromosome loss, establishing that CDC46/MCM5 is required for DNA replication initiation at autonomously replicating sequences (ARSs) during a narrow window at the G1/S transition. Complementation analysis, genetic linkage mapping, minichromosome maintenance assay, DNA content analysis Proceedings of the National Academy of Sciences of the United States of America High 1438234
1993 Fission yeast nda4+ (ortholog of CDC46/MCM5) is essential for viability; nda4 mutants block DNA synthesis onset at the restrictive temperature with a reversible S-phase arrest, and the phenotype is partly rescued by Ca2+, indicating nda4+/MCM5 is required for DNA replication initiation. Temperature-sensitive mutant analysis, DNA content analysis (FACS), gene disruption, complementation Molecular biology of the cell High 8298187
1995 Mouse CDC46/MCM5 protein physically interacts with mouse P1MCM3 (MCM3), as demonstrated by immunochemical co-precipitation, and the genes are expressed in a cell-cycle-specific manner peaking at late G1 to S phase. Co-immunoprecipitation, cell-cycle expression analysis Nucleic acids research Medium 7610039
1996 Human hCdc46/MCM5 protein is composed of 734 amino acids with a central region ~80% identical to yeast Cdc46; immunoprecipitation with hCdc46-specific antibodies shows that essentially all nuclear hCdc46 forms a stable dimeric complex with P1MCM3, and the gene maps to chromosome 22q13.1→q13.2. cDNA cloning, immunoprecipitation, FISH chromosomal mapping Cytogenetics and cell genetics Medium 8751386
1997 A recessive mutation in MCM5/CDC46 (mcm5-bob1, P83L) bypasses the requirement for the S-phase kinase Cdc7p and its cofactor Dbf4p, indicating that Mcm5p normally blocks initiation of DNA replication in the absence of Cdc7p activity, and that Cdc7p acts by relieving this block. Genetic suppressor screen, epistasis analysis in S. cerevisiae Proceedings of the National Academy of Sciences of the United States of America High 9096361
1998 MCM5 directly interacts with the C-terminal transcription activation domain (TAD) of Stat1alpha in a Ser727- and Leu724-dependent manner, both in vitro and in vivo; phosphorylation of Ser727 enhances this interaction. Overexpression of MCM5 enhances Stat1alpha-mediated transcriptional activation in a Ser727-dependent manner, and changes in nuclear MCM5 levels during the cell cycle correlate with the transcriptional response to IFN-gamma. In vitro binding assay, co-immunoprecipitation, transient overexpression/reporter assay, mass spectrometry identification The EMBO journal High 9843502
1999 Human MCM5 gene expression is induced by serum stimulation and regulated by the transcription factor E2F; mutations in E2F binding sites in the MCM5 promoter abolish growth-stimulated and E2F-driven promoter activity, and forced E2F1 expression induces endogenous MCM5 mRNA. Promoter-reporter assay with E2F site mutations, exogenous E2F1 expression, serum stimulation Oncogene High 10327050
2000 Cdc6 is required to load Mcm5 onto replication origins; a cdc6-1 mutant (G260D in the CDC-NTP motif) fails to load Mcm5 onto replication origins by chromatin immunoprecipitation. Furthermore, wild-type Cdc6 promotes the unloading of Mcm5 from chromatin, suggesting Cdc6 controls both loading and unloading of MCM5 to prevent re-replication. Chromatin immunoprecipitation (ChIP), chromatin fractionation, temperature-sensitive mutant analysis in S. cerevisiae DNA and cell biology Medium 10945234
2001 Two specific residues in MCM5 (R732 and K734) are required for direct interaction with the Stat1 TAD both in vitro and in vivo; MCM5-R732A/K734A mutants neither enhance Stat1-mediated transcription nor form complexes with other MCM proteins in vivo. MCM3 does not interact directly with Stat1 but co-purifies with Stat1 via MCM5, demonstrating that Stat1 recruits an MCM5/MCM3 subcomplex. MCM5 ATPase and helicase domain mutations also abolish enhancement of Stat1 activity. In vitro binding assay with site-directed mutagenesis, co-immunoprecipitation, gel filtration of nuclear extracts, transcription reporter assay Proceedings of the National Academy of Sciences of the United States of America High 11248027
2002 The mcm5-bob1 bypass of Cdc7p/Dbf4p requires both Cdk1/Clb5 and Cdk1/Clb2 for DNA replication to occur; loss of either cyclin suppresses bypass. The mcm5-bob1 protein constitutively loads Cdc45 at early origins even in G1-arrested cells (without either kinase active), indicating that mcm5-bob1 adopts a conformation that permits stable Cdc45 binding but that subsequent replication still requires Cdk1 activity. Genetic epistasis with cyclin deletions, ChIP for Cdc45 at origins in arrested cells Genetics High 12019222
2005 MCM5 is inducibly recruited to Stat1 target gene promoters upon IFN-gamma stimulation (shown by ChIP); MCM proteins travel with RNA polymerase II during transcription elongation. An independent domain in MCM5 mediates interaction with Stat1; its overexpression disrupts the interaction and inhibits Stat1 activity. RNAi knockdown of MCM5 abolishes transcription activation of Stat1 target genes, demonstrating that MCM5 is essential for Stat1-mediated transcription in addition to DNA replication. Chromatin immunoprecipitation (ChIP), RNAi knockdown, domain overexpression (dominant-negative), transcription reporter assay Proceedings of the National Academy of Sciences of the United States of America High 16199513
2007 The mcm5-bob1 (P83L) mutation reduces intrinsic firing efficiency at multiple replication origins; an intragenic suppressor mutation predicted by the archaeal MCM structure to interact with P83L reverts the bypass phenotype, indicating that Mcm5 conformation controlled by DDK (Cdc7-Dbf4) phosphorylation determines origin firing efficiency. Mcm5 is proposed as a unique final target of DDK regulation, as analogous mutations in mcm2 and mcm4 cannot bypass DDK. 2D gel analysis of replication intermediates at 11 origins, intragenic suppressor genetics, structural modeling based on archaeal MCM Molecular and cellular biology High 17724082
2007 MCM2-7 and MCM467 both bind single-stranded DNA (ssDNA) in an ATP-dependent manner; the rate of MCM2-7/ssDNA association is slow compared to MCM467, and this slow rate is dramatically increased by preincubation with ATP or by mutations that ablate the MCM2/MCM5 active site, indicating that the MCM2/5 ATPase active site acts as a regulatory gate controlling DNA access to the helicase. In vitro ATPase assay, ssDNA and dsDNA binding assays with purified S. cerevisiae MCM2-7 and MCM467 complexes, electron microscopy (toroidal structure verification) The Journal of biological chemistry High 17895243
2007 Drosophila mcm5 is required for meiotic recombination: a viable allele (mcm5-A7) specifically impairs resolution of meiotic double-strand breaks (DSBs) into crossovers without affecting DSB formation/repair or somatic DNA repair. A null allele causes lethality at third instar larva stage, blocking mitotic but not endo-reduplication events. Genetic analysis: null allele and hypomorphic allele characterization, meiotic recombination frequency, cytological DSB assay (gamma-H2AX), somatic DNA repair assay in Drosophila Genetics Medium 17565942
2008 Cyclin E directly interacts with MCM5 in a centrosomal localization sequence (CLS)-dependent but Cdk2-independent manner, and co-localizes with MCM5 on centrosomes. The interaction domain in MCM5 is distinct from previously known functional domains and is conserved from yeast to mammals. Expression of MCM5 or its cyclin E-interacting domain inhibits centrosome over-duplication in S-phase-arrested CHO cells, indicating MCM5 restrains centrosome re-duplication. Co-immunoprecipitation, cyclin E CLS deletion/mutation analysis, centrosome duplication assay in CHO cells (S-phase arrest), immunofluorescence colocalization Journal of cell science High 18799789
2008 Beta-hairpin domain mutations in yeast Mcm5 cause defects in G1/S transition, DNA replication initiation, and reduced binding of the MCM2-7 complex to replication origins; a synthetically lethal interaction with an analogous mcm4 beta-hairpin mutation confirms a positive role for Mcm5 in origin binding requiring coordination of all six MCM subunits. Site-directed mutagenesis guided by archaeal MCM crystal structure, ChIP at origins, cell cycle analysis, synthetic lethality in S. cerevisiae Genetics High 18660534
2010 Cyclin A interacts with MCM5 and Orc1 at centrosomes via its CLS in a Cdk-independent manner; the same domain in MCM5 that mediates interaction with cyclin E also binds cyclin A, causing centrosomal localization of MCM5. MCM5-mediated inhibition of centrosome re-duplication in S-phase-arrested CHO cells does not require binding to other MCM family members. Co-immunoprecipitation, cyclin A CLS mutant analysis, immunofluorescence, centrosome duplication assay in S-phase-arrested CHO cells Journal of cell science High 20663915
2010 Mutational analysis of Walker B box and arginine finger motifs in each MCM2-7 active site confirms that the MCM5/3 and MCM6/2 ATPase active sites modulate the activity of the MCM2/5 gate, supporting a model in which heterohexameric active sites contribute unequally to helicase function. In vitro ATPase and helicase assays with Walker B and arginine finger mutations in reconstituted S. cerevisiae MCM2-7 complex Nucleic acids research High 20484375
2016 BRD4 directly binds the MCM5 gene locus (shown by ChIP), and BET inhibitors reduce MCM5 mRNA and protein expression in anaplastic thyroid cancer cells; MCM5 silencing reduces cell proliferation, phenocopying BET inhibitor effects. ChIP for BRD4 at MCM5 promoter, BET inhibitor treatment, siRNA knockdown, cell viability assay Endocrine-related cancer Medium 26911376
2016 SOX10 directly activates MCM5 transcription by binding to conserved SOX10 consensus DNA sequences in the MCM5 promoter; knockdown of Sox10 reduces MCM5 expression and inhibits melanocyte proliferation, and this proliferation defect is partially rescued by MCM5 overexpression. SOX10 promoter binding (reporter assay/ChIP implied), RNAi knockdown, overexpression rescue, cell proliferation assay in mouse melanocytes Journal of dermatological science Medium 27955842
2016 MCM5 is incorporated into HIV-1 virions through association with Gag polyprotein; depletion of virion-associated MCM5 reduces reverse transcription efficiency in newly infected cells without affecting integration or downstream replication, indicating MCM5 acts as an inhibitory factor interfering with production of integration-competent cDNA. Co-immunoprecipitation (MCM5-Gag), virion protein analysis, knockdown/depletion experiments, reverse transcription and integration quantification Virology Medium 27414250
2017 Biallelic mutations in MCM5 (a missense in a conserved helicase domain, and a frameshift causing premature stop) cause Meier-Gorlin syndrome; complementation experiments in yeast showed the missense variant cannot rescue lethal mcm5 deletion; patient cells show delayed cell cycle progression. MCM5 depletion in zebrafish causes growth restriction phenotype overlapping that of orc1 depletion. Whole-exome sequencing, yeast complementation assay, cell cycle analysis in patient cells, zebrafish morpholino knockdown European journal of human genetics High 28198391
2021 lnc-POP1-1 directly binds to MCM5 protein and inhibits its ubiquitination and degradation, thereby stabilizing MCM5 and facilitating DNA damage repair caused by cisplatin in HNSCC cells. RNA pulldown/RIP (lncRNA-protein interaction), ubiquitination assay, western blot for MCM5 stability, cisplatin sensitivity assay Molecular therapy Medium 34111560
2021 MCM5 interacts with HDAC1; overexpression of both MCM5 and HDAC1 promotes EMT-dependent proliferation and invasion in lung cancer cells in vitro and tumor growth and metastasis in vivo; blocking the MCM5-HDAC1 interaction with astragaloside IV inhibits these malignant behaviors. Co-immunoprecipitation (MCM5-HDAC1 interaction), overexpression and knockdown in cell lines, in vivo xenograft, pharmacological inhibition with astragaloside IV Frontiers in cell and developmental biology Low 34409025
2022 Drosophila Mcm5 is specifically required for BMP retrograde signaling in the Tv4/FMRFa neuron; Mcm5 loss (and loss of other MCM2-7 components) impairs Tkv (type I BMP receptor) expression and FMRFa neuron specification without detectably reducing progenitor proliferation, indicating a replication-independent role for the MCM2-7 complex in neuronal subtype specification. Genetic loss-of-function in Drosophila CNS, immunofluorescence for neuronal markers, BMP pathway component expression analysis PLoS genetics Medium 35737938
2022 In zebrafish, mcm5 overexpression delays endodermal migration and causes liver bifida by repressing cxcr4a expression, which in turn decreases itgb1b expression; this function is cell cycle-independent, as only mcm5 loss (not overexpression) causes cell cycle delay. Zebrafish overexpression and morpholino knockdown, liver morphology assay, cell cycle analysis, gene expression analysis (cxcr4a, itgb1b) Biomolecules Medium 35204787
2023 IGF2BP3 recognizes m6A-modified MCM5 mRNAs and prolongs their stability, upregulating MCM5 protein; elevated MCM5 competitively inhibits SIRT1-mediated deacetylation of Notch1 intracellular domain (NICD1), stabilizing NICD1 and activating Notch signaling to promote partial EMT and LUAD metastasis. m6A-RIP, RNA stability assay, Co-IP (MCM5-SIRT1-NICD1), NICD1 acetylation/deacetylation assay, MCM5 overexpression/knockdown, in vitro and in vivo metastasis models Advanced science Medium 37171793
2023 Phase-separated DDX21 binds the MCM5 gene locus at high density; disruption of DDX21 phase separation (IDR mutations) markedly reduces DDX21 occupancy at MCM5 and decreases MCM5 expression; ectopic MCM5 expression rescues the impaired migration/invasion phenotype of DDX21-depleted CRC cells, placing MCM5 as a key downstream effector of DDX21-driven EMT. ChIP-seq (DDX21 at MCM5 locus), in vitro phase separation assay with IDR mutants, MCM5 rescue experiment, migration/invasion assays Oncogene Medium 37029300
2025 Cryo-EM structure of an ORC-Cdc6-Cdt1-MCM2-7 intermediate reveals that the Mcm5 C-terminus (C5) contacts Orc3 and specifically recognizes the fully-closed Mcm2/Mcm5 ring interface. Normal MCM2-7 loading triggers Mcm4 ATP hydrolysis, which reorganizes the complex and releases Cdt1; mutations at the Mcm2/Mcm5 interface impair ring closure, prevent productive ATP hydrolysis, and cause complex disassembly, identifying Mcm4 as the key ATPase regulating pre-RC formation. Cryo-EM structure determination, site-directed mutagenesis of Mcm2/Mcm5 interface, ATPase assay, helicase loading assay Nature communications High 39747125
2025 UFL1, the UFM1 E3 ligase, catalyzes UFMylation of MCM5 at Lys583; mutation of Lys583 destabilizes the CMG helicase complex, delays replication origin firing, and slows replication fork progression. All MPD-associated mutations in UFMylation enzymes impair DNA replication, connecting MCM5 UFMylation to both efficient replication and prevention of microcephalic primordial dwarfism. In vitro UFMylation assay, Lys583 site-directed mutagenesis, DNA fiber assay (replication fork speed), origin firing assay, CMG complex stability analysis The EMBO journal High 40940420
2025 In zebrafish mcm5 mutants, Mcm5 loss causes DNA damage in immature T lymphocytes and accelerated apoptosis; mechanistically, Mcm5 directly binds Stat1a and facilitates its phosphorylation to enhance bcl2a transcription under DNA replication stress; loss of the Mcm5-Stat1 complex reduces Stat1 phosphorylation and bcl2a expression, accelerating apoptosis. This Mcm5-Stat1-Bcl2 role in T cell development is conserved in mice. Zebrafish mcm5 mutant analysis, co-immunoprecipitation (Mcm5-Stat1), Stat1 phosphorylation assay, bcl2 expression analysis, mouse model validation Cell death & disease Medium 39929806
2023 The novel peptide PFAP1 binds MCM5 protein in newborn mouse ovaries, inhibits MCM5 ubiquitination and degradation, and promotes granulosa cell proliferation and primordial follicle activation, establishing MCM5 as a functional target of PFAP1 in ovarian biology. Mass spectrometry identification of PFAP1, Co-IP/pulldown (PFAP1-MCM5 interaction), ubiquitination assay, in vitro follicle activation, in vivo aged mouse fertility assay FASEB journal Low 37086099

Source papers

Stage 0 corpus · 71 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 mcm5/cdc46-bob1 bypasses the requirement for the S phase activator Cdc7p. Proceedings of the National Academy of Sciences of the United States of America 222 9096361
1990 Subcellular localization of yeast CDC46 varies with the cell cycle. Genes & development 208 2279699
2005 p16INK4A, CDC6, and MCM5: predictive biomarkers in cervical preinvasive neoplasia and cervical cancer. Journal of clinical pathology 187 15858126
1998 Ser727-dependent recruitment of MCM5 by Stat1alpha in IFN-gamma-induced transcriptional activation. The EMBO journal 178 9843502
1999 Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F. Oncogene 128 10327050
2011 MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival. Cell death and differentiation 127 21233845
1992 CDC46/MCM5, a yeast protein whose subcellular localization is cell cycle-regulated, is involved in DNA replication at autonomously replicating sequences. Proceedings of the National Academy of Sciences of the United States of America 93 1438234
1999 Immunoassay for urothelial cancers that detects DNA replication protein Mcm5 in urine. Lancet (London, England) 87 10551502
2008 Clinical significance of MCM-2 and MCM-5 expression in colon cancer: association with clinicopathological parameters and tumor proliferative capacity. Digestive diseases and sciences 84 18465232
2001 Identification of two residues in MCM5 critical for the assembly of MCM complexes and Stat1-mediated transcription activation in response to IFN-gamma. Proceedings of the National Academy of Sciences of the United States of America 76 11248027
1993 Fission yeast genes nda1+ and nda4+, mutations of which lead to S-phase block, chromatin alteration and Ca2+ suppression, are members of the CDC46/MCM2 family. Molecular biology of the cell 76 8298187
2005 The DNA replication factor MCM5 is essential for Stat1-mediated transcriptional activation. Proceedings of the National Academy of Sciences of the United States of America 74 16199513
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
2017 MCM5: a new actor in the link between DNA replication and Meier-Gorlin syndrome. European journal of human genetics : EJHG 67 28198391
2007 Differences in the single-stranded DNA binding activities of MCM2-7 and MCM467: MCM2 and MCM5 define a slow ATP-dependent step. The Journal of biological chemistry 66 17895243
2023 Phase separation of DDX21 promotes colorectal cancer metastasis via MCM5-dependent EMT pathway. Oncogene 60 37029300
2023 m6 A-Dependent Modulation via IGF2BP3/MCM5/Notch Axis Promotes Partial EMT and LUAD Metastasis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 60 37171793
2010 The cyclin A centrosomal localization sequence recruits MCM5 and Orc1 to regulate centrosome reduplication. Journal of cell science 54 20663915
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
2021 lncRNA lnc-POP1-1 upregulated by VN1R5 promotes cisplatin resistance in head and neck squamous cell carcinoma through interaction with MCM5. Molecular therapy : the journal of the American Society of Gene Therapy 48 34111560
2010 The Saccharomyces cerevisiae Mcm6/2 and Mcm5/3 ATPase active sites contribute to the function of the putative Mcm2-7 'gate'. Nucleic acids research 47 20484375
2009 Dynamic localization of the DNA replication proteins MCM5 and MCM7 in plants. Plant physiology 44 19357199
2010 MCM-2 and MCM-5 expression in gastric adenocarcinoma: clinical significance and comparison with Ki-67 proliferative marker. Digestive diseases and sciences 43 20694513
2008 Cyclin E-dependent localization of MCM5 regulates centrosome duplication. Journal of cell science 43 18799789
2016 MCM5 as a target of BET inhibitors in thyroid cancer cells. Endocrine-related cancer 42 26911376
2005 Quantitation of CDC6 and MCM5 mRNA in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the cervix. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 42 15696126
2007 Structural changes in Mcm5 protein bypass Cdc7-Dbf4 function and reduce replication origin efficiency in Saccharomyces cerevisiae. Molecular and cellular biology 41 17724082
1995 Cdc54 belongs to the Cdc46/Mcm3 family of proteins which are essential for initiation of eukaryotic DNA replication. Gene 38 7698653
2012 Bladder cancer diagnosis and identification of clinically significant disease by combined urinary detection of Mcm5 and nuclear matrix protein 22. PloS one 32 22792272
2002 The mcm5-bob1 bypass of Cdc7p/Dbf4p in DNA replication depends on both Cdk1-independent and Cdk1-dependent steps in Saccharomyces cerevisiae. Genetics 31 12019222
2018 MiR-362-3p functions as a tumor suppressor through targeting MCM5 in cervical adenocarcinoma. Bioscience reports 28 29871972
1998 Reduced expression of pax-3 is associated with overexpression of cdc46 in the mouse embryo. Development genes and evolution 28 9601985
2020 Diagnostic Accuracy of MCM5 for the Detection of Recurrence in Nonmuscle Invasive Bladder Cancer Followup: A Blinded, Prospective Cohort, Multicenter European Study. The Journal of urology 26 32314931
2020 Detection of MCM5 as a novel non-invasive aid for the diagnosis of endometrial and ovarian tumours. BMC cancer 25 33059604
2007 A genetic analysis of the Drosophila mcm5 gene defines a domain specifically required for meiotic recombination. Genetics 25 17565942
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
2021 MCM5 Aggravates the HDAC1-Mediated Malignant Progression of Lung Cancer. Frontiers in cell and developmental biology 23 34409025
2016 Sox10 regulates skin melanocyte proliferation by activating the DNA replication licensing factor MCM5. Journal of dermatological science 19 27955842
2008 Functional conservation of beta-hairpin DNA binding domains in the Mcm protein of Methanobacterium thermoautotrophicum and the Mcm5 protein of Saccharomyces cerevisiae. Genetics 18 18660534
2022 Label-free electrochemical immunosensor for picomolar detection of the cervical cancer biomarker MCM5. Analytica chimica acta 17 36038236
2021 CRNDE enhances the expression of MCM5 and proliferation in acute myeloid leukemia KG-1a cells by sponging miR-136-5p. Scientific reports 16 34408205
2019 MCM5 Expression Is Associated With the Grade of Malignancy and Ki-67 Antigen in LSCC. Anticancer research 16 31092424
2021 MCM5 urine expression (ADXBLADDER) is a reliable biomarker of high-risk non- muscle-invasive bladder cancer recurrence: A prospective matched case-control study. Cancer biomarkers : section A of Disease markers 15 32924986
2020 Predictive value of MCM5 (ADXBLADDER) analysis in urine of men evaluated for the initial diagnosis of bladder cancer: A comparative prospective study. Diagnostic cytopathology 15 32562513
2016 Loss of ncm5 and mcm5 wobble uridine side chains results in an altered metabolic profile. Metabolomics : Official journal of the Metabolomic Society 15 27738410
2016 Cancer-specific promoters for expression-targeted gene therapy: ran, brms1 and mcm5. The journal of gene medicine 14 27140445
2018 Significance of DNA Replication Licensing Proteins (MCM2, MCM5 and CDC6), p16 and p63 as Markers of Premalignant Lesions of the Uterine Cervix: Its Usefulness to Predict Malignant Potential. Asian Pacific journal of cancer prevention : APJCP 12 29373905
2024 MEG3 shuttled by exosomes released from human bone marrow mesenchymal stem cells promotes TP53 stability to regulate MCM5 transcription in keloid fibroblasts. The journal of gene medicine 10 38686583
2022 Diagnostic performance of minichromosome maintenance 5 (MCM5) in bladder cancer: A systematic review and meta-analysis. Urologic oncology 10 35414492
1996 Coding sequence and chromosome mapping of the human gene (CDC46) for replication protein hCdc46/Mcm5. Cytogenetics and cell genetics 9 8751386
2023 MCM5 is an oncogene of colon adenocarcinoma and promotes progression through cell cycle control. Acta histochemica 8 37385108
2025 MCM2-7 ring closure involves the Mcm5 C-terminus and triggers Mcm4 ATP hydrolysis. Nature communications 7 39747125
2019 Diagnosis of urinary bladder urothelial carcinoma by immunocytology with p53, MCM5, MCM2 and Ki-67 antibodies using cell blocks derived from urine. Cytopathology : official journal of the British Society for Clinical Cytology 7 30943322
2009 Analysis of pRb, p16INK4A proteins and proliferating antigens: PCNA, Ki-67 and MCM5 expression in aggressive fibromatosis (desmoid tumor). Histology and histopathology 6 19130399
2023 MTA2 is one of 14 Transcription factors predicting recurrence free survival in gastric cancer and promotes cancer progression by targeting MCM5. Journal of Cancer 5 36741260
2000 Loss control of Mcm5 interaction with chromatin in cdc6-1 mutated in CDC-NTP motif. DNA and cell biology 5 10945234
2016 Cellular minichromosome maintenance complex component 5 (MCM5) is incorporated into HIV-1 virions and modulates viral replication in the newly infected cells. Virology 4 27414250
2024 MCM5 is a Novel Therapeutic Target for Glioblastoma. OncoTargets and therapy 3 38765057
2023 The novel peptide PFAP1 promotes primordial follicle activation by binding to MCM5. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 3 37086099
2022 Mcm5 Represses Endodermal Migration through Cxcr4a-itgb1b Cascade Instead of Cell Cycle Control. Biomolecules 3 35204787
2021 [lncRNA CRNDE promotes proliferation and inhibits apoptosis of U937 cells by downregulating miR-136-5p and upregulating MCM5]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 3 34809738
2025 Mcm5 mutation leads to silencing of Stat1-bcl2 which accelerating apoptosis of immature T lymphocytes with DNA damage. Cell death & disease 2 39929806
2025 TFAP4 Regulation of MCM5 Activates the PI3K/AKT Pathway to Promote Invasion and Metastasis of Gastric Cancer. Digestive diseases and sciences 2 39971831
2025 MCM5 UFMylation regulates replication origin firing and fork progression. The EMBO journal 2 40940420
2022 Selective role of the DNA helicase Mcm5 in BMP retrograde signaling during Drosophila neuronal differentiation. PLoS genetics 1 35737938
2019 Minichromosomal Maintenance Component Complex 5 (MCM5) as a Marker of Barrett's Esophagus-Related Neoplasia: A Feasibility Study. Digestive diseases and sciences 1 30982210
2025 Diabetes is causally associated with increased breast cancer mortality by inducing FIBCD1 to activate MCM5-mediated cell cycle arrest via modulating H3K27ac. Cell death & disease 0 40695783
2025 ‌Liquid-Liquid Phase Separation of AR Orchestrated by Melatonin Sensitizes Prostate Cancer to Ferroptosis Via MCM5/NRF2 Axis Collapse. Journal of pineal research 0 41159313
2025 Comprehensive Bioinformatics and Functional Analysis Identified MCM5 Facilitates Glioblastoma Progression Through Cell Cycle Regulation. Biochemical genetics 0 41296143
2025 Quantitative LFQ-DIA proteomics reveals FTH1-MCM5/WNT axis mediated osteoblastic dysfunction via ferroptosis drives diabetic osteoporosis. Scientific reports 0 41372273
2025 SPP1, LYZ, and MCM5: potential diagnostic biomarkers for rheumatoid arthritis and cervical cancer comorbidity. Frontiers in medicine 0 41384115

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