Affinage

MCM5

DNA replication licensing factor MCM5 · UniProt P33992

Length
734 aa
Mass
82.3 kDa
Annotated
2026-04-28
71 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MCM5 is a core subunit of the MCM2-7 replicative helicase complex essential for DNA replication initiation and elongation in eukaryotes. Within the hexameric ring, MCM5 forms a regulated gate with MCM2 that controls DNA entry during origin licensing; this Mcm2/5 interface is remodeled to a closed state during ORC-Cdc6-Cdt1-mediated loading, and MCM5 serves as a key regulatory target of DDK kinase (Cdc7-Dbf4), whose requirement can be bypassed by the MCM5-P83L conformational mutation (PMID:17895243, PMID:39747125, PMID:9096361). UFMylation of MCM5 at Lys583 by UFL1 stabilizes the CMG helicase complex and is required for efficient origin firing and fork progression (PMID:40940420). Beyond replication, MCM5 directly binds STAT1 via residues R732/K734 and is recruited to cytokine-responsive gene promoters where it is essential for STAT1-mediated transcription activation and T cell survival through a Stat1-Bcl2 axis; it also interacts with cyclins A/E at centrosomes to prevent reduplication, and biallelic loss-of-function mutations cause Meier-Gorlin syndrome (PMID:11248027, PMID:16199513, PMID:39929806, PMID:18799789, PMID:28198391).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1990 High

    Establishing that MCM5 nuclear access is cell-cycle regulated answered whether the MCM licensing system restricts replication to once per cycle via protein relocalization.

    Evidence Cell fractionation and immunolocalization of CDC46/MCM5 across yeast cell cycle stages

    PMID:2279699

    Open questions at the time
    • Mechanism of nuclear exclusion at S-phase not defined
    • Whether relocalization is cause or consequence of replication restriction unclear
  2. 1992 High

    Confirming CDC46 identity with MCM5 and its requirement at origins during G1/S established MCM5 as a bona fide replication initiation factor.

    Evidence Complementation analysis and minichromosome maintenance assay in yeast

    PMID:1438234 PMID:8298187

    Open questions at the time
    • Biochemical activity of MCM5 at origins unknown
    • Whether MCM5 acts alone or in a complex not yet determined
  3. 1996 Medium

    Demonstrating that MCM5 forms a stable nuclear dimer with MCM3 in mouse and human cells established the first defined subcomplex within what would become the MCM2-7 hexamer.

    Evidence Co-immunoprecipitation in mouse and human cells with CDC46-specific antibodies

    PMID:7610039 PMID:8751386

    Open questions at the time
    • Single Co-IP approach without reciprocal validation in early studies
    • Full hexameric composition not yet established
    • Functional significance of MCM5-MCM3 dimer unclear
  4. 1997 High

    The bob1 (P83L) suppressor mutation bypassing DDK requirement revealed that MCM5 is the critical regulatory gate that DDK phosphorylation must open for replication to initiate.

    Evidence Genetic suppressor screen identifying mcm5-bob1 as bypass of cdc7/dbf4 in yeast

    PMID:9096361

    Open questions at the time
    • Structural basis for how P83L mimics DDK phosphorylation unknown
    • Direct phosphorylation sites on MCM5 not mapped
  5. 1998 High

    Discovery that MCM5 directly binds STAT1's transcription activation domain and enhances IFN-γ-responsive transcription revealed an unexpected replication-independent function as a transcriptional coactivator.

    Evidence In vitro binding, Co-IP, and transcription reporter assays in IFN-γ-stimulated cells

    PMID:9843502

    Open questions at the time
    • Whether this function operates in vivo at endogenous loci unknown
    • Mechanism by which MCM5 activates transcription not defined
  6. 2000 Medium

    Showing that Cdc6 controls both loading and unloading of MCM5 at origins placed MCM5 downstream of ORC-Cdc6 in the licensing pathway.

    Evidence ChIP and chromatin fractionation using cdc6-1 temperature-sensitive mutants in yeast

    PMID:10945234

    Open questions at the time
    • Single lab study
    • Whether Cdc6 acts directly on MCM5 or through the whole hexamer not resolved
  7. 2001 High

    Mapping MCM5 residues R732/K734 as essential for both STAT1 binding and MCM3 complex formation, and showing MCM5 bridges STAT1 to the MCM5/MCM3 subcomplex, defined the molecular interface for MCM5's transcriptional role.

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

    PMID:11248027

    Open questions at the time
    • Whether STAT1 and MCM complex binding are mutually exclusive not resolved
    • In vivo chromatin occupancy not tested
  8. 2002 High

    Dissecting mcm5-bob1 epistasis with CDK showed that DDK and CDK act at distinct replication initiation steps, with bob1 bypassing only the DDK-dependent Cdc45 loading step.

    Evidence Double mutant analysis combined with ChIP for Cdc45 loading at origins in yeast

    PMID:12019222

    Open questions at the time
    • Structural basis for how bob1 enables Cdc45 loading remains unclear
    • Whether bob1 affects all origins equally not fully resolved
  9. 2005 High

    ChIP demonstration that MCM5 is recruited to STAT1 target promoters upon cytokine stimulation and tracks with RNA Pol II, combined with RNAi showing MCM5 is essential for this transcription, established MCM5 as an obligate transcriptional cofactor at endogenous loci.

    Evidence ChIP across STAT1 target genes and RNAi knockdown of MCM5 in cytokine-stimulated cells

    PMID:16199513

    Open questions at the time
    • Whether MCM5 has helicase activity during transcription unknown
    • Genome-wide extent of transcriptional role not mapped
  10. 2007 High

    Biochemical and structural studies revealed that the Mcm2/5 interface acts as a regulated DNA entry gate whose opening is controlled by ATP hydrolysis, while bob1 introduces conformational heterogeneity reducing origin firing efficiency, unifying the gate and regulatory models.

    Evidence In vitro ssDNA/dsDNA binding with ATPase mutants; origin efficiency analysis by 2D gel with intragenic suppressor genetics

    PMID:17724082 PMID:17895243

    Open questions at the time
    • No high-resolution structure of the open gate state
    • Regulation of gate opening by post-translational modifications not characterized
  11. 2007 High

    A Drosophila mcm5 allele specifically impaired meiotic crossover resolution without affecting DNA repair, revealing a separable meiosis-specific function.

    Evidence Genetic analysis with hypomorphic alleles measuring recombination frequency vs. DSB repair in Drosophila

    PMID:17565942

    Open questions at the time
    • Biochemical mechanism of MCM5 in crossover resolution unknown
    • Whether this function is conserved in mammals not tested
  12. 2008 High

    MCM5 interacts with cyclins E and A via a CLS-dependent domain distinct from its MCM complex interface, localizing MCM5 to centrosomes where it inhibits reduplication, establishing a replication-independent role in centrosome licensing.

    Evidence Co-IP, domain mapping, colocalization microscopy, and centrosome reduplication assay in CHO cells

    PMID:18799789 PMID:20663915

    Open questions at the time
    • Whether centrosomal MCM5 function requires helicase activity unknown
    • Mechanism of reduplication inhibition not defined
  13. 2010 High

    Systematic mutagenesis of all six ATPase active sites in the MCM2-7 ring established a hierarchical architecture where the Mcm5/3 and Mcm6/2 sites modulate the Mcm2/5 gate.

    Evidence Walker B and arginine finger mutagenesis with in vitro ATPase and helicase assays

    PMID:20484375

    Open questions at the time
    • How hierarchy translates to in vivo origin activation kinetics not known
    • Contribution of accessory factors (GINS, Cdc45) to this hierarchy not tested
  14. 2017 High

    Identification of biallelic MCM5 mutations causing Meier-Gorlin syndrome, with yeast complementation failure and zebrafish phenocopy, established MCM5 as a disease gene for primordial dwarfism.

    Evidence Whole-exome sequencing of patient, yeast complementation, patient cell cycle analysis, zebrafish morpholino knockdown

    PMID:28198391

    Open questions at the time
    • Genotype-phenotype correlation for different MCM5 alleles not established
    • Whether transcriptional functions of MCM5 contribute to disease phenotype unknown
  15. 2023 High

    MCM5 was shown to competitively inhibit SIRT1-mediated deacetylation of NICD1, activating Notch signaling and EMT, revealing a non-replicative signaling function in cancer metastasis.

    Evidence Co-IP (MCM5-SIRT1-NICD1), deacetylation assay, m6A-RIP for MCM5 mRNA stability, loss-of-function/rescue in LUAD cells

    PMID:37171793

    Open questions at the time
    • Structural basis for MCM5-SIRT1 interaction not defined
    • Whether this is a stoichiometric competition or catalytic mechanism unclear
  16. 2025 High

    Cryo-EM of the ORC-Cdc6-Cdt1-MCM2-7 loading intermediate revealed that the Mcm2/5 interface is remodeled to a closed state during licensing, with the MCM5 C-terminus contacting Orc3, and Mcm4 ATPase activity driving ring closure and Cdt1 release.

    Evidence Cryo-EM structure determination combined with interface mutagenesis and biochemical helicase loading reconstitution

    PMID:39747125

    Open questions at the time
    • Dynamics of gate closure in real time not captured
    • How DDK phosphorylation subsequently reopens or remodels this interface for activation not structurally resolved
  17. 2025 High

    UFMylation of MCM5 at Lys583 by UFL1 was shown to stabilize the CMG helicase and promote origin firing and fork progression, identifying the first essential post-translational modification of MCM5 for replication elongation.

    Evidence In vitro UFMylation assay, K583R mutagenesis, DNA fiber assay, origin firing analysis, Co-IP for CMG stability

    PMID:40940420

    Open questions at the time
    • How UFMylation structurally stabilizes CMG not determined
    • Whether UFMylation is cell-cycle regulated or constitutive unclear
    • Interplay between UFMylation and DDK phosphorylation not tested
  18. 2025 High

    MCM5 binding to Stat1 promotes Stat1 phosphorylation and bcl2a transcription, preventing apoptosis of immature T cells, establishing a replication-independent pro-survival axis conserved in zebrafish and mice.

    Evidence Co-IP of Mcm5-Stat1, phosphorylation and transcription analysis in mcm5 mutant zebrafish and mouse models

    PMID:39929806

    Open questions at the time
    • Which kinase is facilitated by MCM5 for Stat1 phosphorylation unknown
    • Whether this axis operates in other immune cell types not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural mechanism by which DDK phosphorylation and UFMylation coordinately activate the Mcm2/5 gate for CMG assembly; whether MCM5's transcriptional and centrosomal functions contribute to Meier-Gorlin syndrome pathology; and the full genome-wide scope of MCM5's replication-independent transcriptional roles.
  • No structure of DDK-phosphorylated MCM5 within CMG
  • Contribution of non-replicative MCM5 functions to disease unknown
  • Genome-wide ChIP-seq for MCM5 at transcribed loci not reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 4 GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 3 GO:0005815 microtubule organizing center 2
Pathway
R-HSA-69306 DNA Replication 7 R-HSA-1640170 Cell Cycle 4 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 1 R-HSA-5357801 Programmed Cell Death 1
Partners
CCNA2CCNE1CDC6MCM2MCM3SIRT1STAT1UFL1
Complex memberships
CMG (Cdc45-MCM-GINS) helicaseMCM2-7 hexamerORC-Cdc6-Cdt1-MCM2-7 pre-RC

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 Yeast CDC46/MCM5 protein undergoes cell cycle-dependent subcellular relocalization: it accumulates in the nucleus of interphase cells and is rapidly lost from the nucleus at the G1-S boundary coinciding with DNA replication, then re-enters the nucleus as mitosis completes, suggesting nuclear localization restricts DNA replication to once per cell cycle. Cell fractionation and immunolocalization across cell cycle stages Genes & Development High 2279699
1992 CDC46 is identical to MCM5 (confirmed by complementation), and the protein is required for initiation of DNA replication at autonomously replicating sequences (origins), acting during a narrow window at the G1/S transition. Complementation analysis, minichromosome maintenance assay, genetic linkage Proceedings of the National Academy of Sciences High 1438234
1993 Fission yeast nda4+ (MCM5 ortholog) is required for the onset of DNA synthesis; its block is reversible and partly rescued by calcium, and the protein shares a conserved central ATPase-like domain with other MCM family members. Temperature-sensitive mutant analysis, DNA content analysis (flow cytometry), gene disruption Molecular Biology of the Cell High 8298187
1995 Mouse CDC46/MCM5 protein physically interacts with P1MCM3, forming a dimeric complex; both proteins are expressed in a cell-cycle-specific manner peaking at late G1/S. Co-immunoprecipitation, immunochemical analysis Nucleic Acids Research Medium 7610039
1996 Human CDC46/MCM5 protein forms a stable dimeric complex with P1MCM3 in the nucleus, as confirmed by immunoprecipitation with CDC46-specific antibodies; the gene maps to chromosome 22q13.1→q13.2. Immunoprecipitation, cDNA cloning, FISH Cytogenetics and Cell Genetics Medium 8751386
1997 A recessive point mutation in yeast MCM5/CDC46 (P83L, 'bob1') bypasses the requirement for the DDK kinase Cdc7p/Dbf4p for initiation of DNA replication, indicating MCM5 is a key regulatory target of Cdc7p and that in the absence of Cdc7p activity, MCM5 normally blocks replication initiation. Genetic suppressor screen, cell cycle analysis, yeast genetics Proceedings of the National Academy of Sciences High 9096361
1998 MCM5 directly interacts with the transcription activation domain (TAD) of STAT1α in a manner dependent on phosphorylation of STAT1 Ser727 and Leu724; overexpression of MCM5 enhances STAT1-mediated transcriptional activation in response to IFN-γ, and nuclear MCM5 levels correlate with IFN-γ transcriptional response across the cell cycle. In vitro binding assay, co-immunoprecipitation, transient transfection/transcription reporter assay, mass spectrometry identification The EMBO Journal High 9843502
1999 E2F transcription factor directly regulates growth-stimulated expression of human MCM5 (and MCM6) through binding to E2F sites in the MCM5 promoter; mutation of E2F sites abolishes serum-stimulated promoter activity and exogenous E2F1 induces all MCM family members. Promoter mutagenesis, reporter assay, forced E2F expression, serum stimulation Oncogene High 10327050
2000 Yeast Cdc6 is required to load MCM5 onto replication origins; the cdc6-1 mutation (G260D near the CDC-NTP motif) fails to load Mcm5 onto origins and also fails to unload Mcm5 from chromatin, while wild-type Cdc6 overexpression accelerates Mcm5 unloading, indicating Cdc6 controls both loading and unloading of MCM5 at origins. Chromatin immunoprecipitation (ChIP), chromatin fractionation, temperature-sensitive mutant analysis DNA and Cell Biology Medium 10945234
2001 Two specific residues in MCM5 (R732, K734) are required for direct interaction with STAT1 TAD both in vitro and in vivo; mutation of these residues abolishes STAT1-mediated transcription activation. The same residues are also required for MCM5 to form complexes with other MCM proteins (MCM3) in vivo. MCM3 does not interact directly with STAT1 but co-purifies with STAT1 through MCM5, forming a MCM5/MCM3 subcomplex that co-elutes with STAT1 after IFN-γ treatment. Mutagenesis, in vitro binding assay, co-immunoprecipitation, gel filtration, transcription reporter assay Proceedings of the National Academy of Sciences High 11248027
2002 The mcm5-bob1 bypass of Cdc7p/Dbf4p requires both Cdk1/Clb5p and Cdk1/Clb2p activities; the mcm5-bob1 mutation enables constitutive loading of Cdc45p at early origins even in G1-arrested cells without either kinase active, revealing that Cdc7p and Cdk1p act at distinct steps in replication initiation, only a subset of which is bypassed by mcm5-bob1. Genetic epistasis (double mutant analysis), ChIP for Cdc45p loading, overexpression experiments Genetics High 12019222
2005 MCM5 protein is inducibly recruited to STAT1 target gene promoters in response to cytokine stimulation and moves along with RNA polymerase II during transcription elongation; RNAi knockdown of MCM5 abolishes STAT1 target gene transcription activation, demonstrating MCM5 is essential for STAT1-mediated transcription. Chromatin immunoprecipitation (ChIP), RNA interference (RNAi) knockdown, domain overexpression competition assay Proceedings of the National Academy of Sciences High 16199513
2007 The mcm5-bob1 (P83L) mutation reduces intrinsic origin firing efficiency at multiple endogenous origins by causing MCM5 to adopt multiple conformations (predicted from archaeal MCM atomic structure), only one of which is permissive for origin activation; an intragenic suppressor mutation confirms this conformational model. Origin efficiency analysis (2D gel, BrdU incorporation), intragenic suppressor genetics, structural modeling Molecular and Cellular Biology High 17724082
2007 Within the MCM2-7 hexamer, MCM2 and MCM5 define the Mcm2/5 interface which functions as a slow ATP-dependent gate controlling single-stranded DNA entry; mutations ablating the MCM2/5 ATPase active site dramatically accelerate ssDNA association, consistent with the Mcm2/5 interface being a regulated DNA entry gate. In vitro biochemical assay (ssDNA and dsDNA binding), ATPase mutant analysis, electron microscopy (toroidal structure) Journal of Biological Chemistry High 17895243
2008 Cyclin E directly interacts with MCM5 via a specific domain in MCM5 (distinct from its MCM complex-interacting domain) in a CLS-dependent but Cdk2-independent manner; this interaction localizes MCM5 to centrosomes, and expression of MCM5 or its cyclin E-interacting domain significantly inhibits centrosome over-duplication in S-phase-arrested CHO cells. Co-immunoprecipitation, colocalization (microscopy), domain mapping, centrosome reduplication assay in CHO cells Journal of Cell Science High 18799789
2008 Beta-hairpin domains in yeast Mcm5 are essential for DNA binding and for binding of the entire Mcm2-7 complex to replication origins in vivo; mcm5 beta-hairpin mutants display defects at the G1/S transition and a synthetic lethal interaction with a similar mcm4 mutation, revealing a positive role for Mcm5 in origin binding requiring coordination of all six Mcm subunits. Yeast genetics, ChIP (origin binding), cell cycle analysis, synthetic lethality screen Genetics High 18660534
2010 The Mcm2/5 and Mcm5/3 ATPase active sites, defined by Walker B and arginine finger motifs, contribute unequally to MCM2-7 activity; Mcm5/3 and Mcm6/2 active sites modulate the putative Mcm2/5 gate, establishing a hierarchical ATPase functional architecture within the hexamer. Walker B and arginine finger mutagenesis, in vitro ATPase and helicase assays Nucleic Acids Research High 20484375
2010 Cyclin A interacts with MCM5 and Orc1 via its centrosomal localization sequence (CLS) in a Cdk-independent manner; the same domain in MCM5 that mediates cyclin E interaction also binds cyclin A, leading to centrosomal localization of MCM5; MCM5-mediated inhibition of centrosome reduplication does not require binding to other MCM family members. Co-immunoprecipitation, CLS domain mutagenesis, centrosome reduplication assay in CHO cells Journal of Cell Science High 20663915
2007 Drosophila mcm5 has a meiosis-specific function: a viable allele (mcm5-A7) specifically impairs resolution of meiotic double-strand breaks into crossovers without affecting DSB formation/repair or somatic DNA repair, revealing a role for MCM5 in the meiotic recombination pathway distinct from its DNA replication function. Genetic analysis (null and hypomorphic alleles), DSB repair assay, recombination frequency measurement Genetics High 17565942
2011 miR-885-5p directly targets the 3'-UTR of MCM5 (and CDK2) mRNA via predicted binding sites, reducing MCM5 protein expression; enforced miR-885-5p expression inhibits neuroblastoma cell proliferation and activates p53, demonstrating MCM5 is a direct post-transcriptional target of miR-885-5p. 3'-UTR luciferase reporter assay, Western blot, qPCR, gain-of-function miRNA overexpression Cell Death and Differentiation High 21233845
2016 BRD4 directly binds the MCM5 gene locus (shown by ChIP); BET inhibitor treatment reduces MCM5 mRNA and protein; MCM5 silencing reduces proliferation in anaplastic thyroid cancer cells, placing MCM5 downstream of BET/BRD4-driven transcription. Chromatin immunoprecipitation (ChIP), transcriptome analysis, siRNA knockdown, viability assay Endocrine-Related Cancer Medium 26911376
2016 SOX10 directly activates MCM5 transcription by binding conserved SOX10 consensus sequences in the MCM5 promoter; Sox10 knockdown reduces MCM5 expression and inhibits melanocyte proliferation, which is partially rescued by MCM5 overexpression, establishing a SOX10-MCM5 axis controlling melanocyte proliferation. ChIP (SOX10 binding to MCM5 promoter), RNAi knockdown, rescue overexpression, reporter assay Journal of Dermatological Science High 27955842
2016 MCM5 associates with Gag polyprotein and is incorporated into HIV-1 virions; virions depleted of MCM5 show reduced reverse transcription in newly infected cells, while excess MCM5 in virions also reduces reverse transcription, suggesting MCM5 acts as an inhibitory factor interfering with production of integration-competent cDNA. Co-immunoprecipitation (MCM5-Gag), virion incorporation assay, reverse transcription assay in infected cells Virology Medium 27414250
2017 Biallelic mutations in MCM5 (a missense in a conserved helicase domain and a frameshift) cause Meier-Gorlin syndrome; the missense variant fails to complement mcm5 deletion in yeast, demonstrating loss of helicase function; patient cells show delayed cell cycle progression; zebrafish mcm5 depletion recapitulates the growth restriction phenotype. Whole-exome sequencing, yeast complementation assay, cell cycle analysis of patient cells, zebrafish morpholino knockdown European Journal of Human Genetics High 28198391
2021 lnc-POP1-1 directly binds MCM5 protein and inhibits its ubiquitination and degradation, thereby stabilizing MCM5 and facilitating DNA damage repair caused by cisplatin, promoting cisplatin resistance in HNSCC cells. RNA pulldown/RIP, co-immunoprecipitation, ubiquitination assay, Western blot Molecular Therapy Medium 34111560
2023 IGF2BP3 binds m6A-modified MCM5 mRNA to prolong its stability, upregulating MCM5 protein, which competitively inhibits SIRT1-mediated deacetylation of Notch1 intracellular domain (NICD1), thereby stabilizing NICD1 and activating Notch signaling to promote partial EMT and LUAD metastasis. m6A-RIP, RNA stability assay, Co-IP (MCM5-SIRT1-NICD1), deacetylation assay, loss-of-function/rescue experiments Advanced Science High 37171793
2023 Phase-separated DDX21 binds the MCM5 gene locus to drive MCM5 transcription; disruption of DDX21 phase separation (IDR mutations) reduces MCM5 expression; ectopic MCM5 expression rescues the impaired metastatic ability of DDX21-depleted colorectal cancer cells, placing MCM5 as a key downstream effector of DDX21 in EMT/metastasis. ChIP (DDX21 at MCM5 locus), phase separation assay, IDR mutagenesis, ectopic expression rescue, in vivo metastasis model Oncogene High 37029300
2025 Cryo-EM structure of an ORC-Cdc6-Cdt1-MCM2-7 loading intermediate reveals that the Mcm2/Mcm5 interface undergoes remodeling to a fully closed state; the MCM5 C-terminus (C5) contacts Orc3 and specifically recognizes this closed ring; normal helicase loading triggers Mcm4 ATP hydrolysis leading to MCM2-7 reorganization and Cdt1 release; mutations disrupting the Mcm2/Mcm5 interface cause ring splitting and complex disassembly, identifying Mcm4 as the key ATPase for pre-RC formation. Cryo-EM structure determination, mutagenesis of Mcm2/Mcm5 interface, biochemical helicase loading assay, ATPase mutant analysis Nature Communications High 39747125
2025 UFL1 (UFM1 E3 ligase) catalyzes UFMylation of MCM5 at Lys583; mutation of Lys583 blocking this modification destabilizes the CMG helicase complex, delays origin firing, and slows replication fork progression, establishing UFMylation of MCM5 as essential for efficient DNA replication. In vitro UFMylation assay, site-directed mutagenesis (K583R), DNA fiber assay (fork progression), origin firing analysis, co-immunoprecipitation (helicase complex stability) The EMBO Journal High 40940420
2025 In zebrafish, Mcm5 directly binds Stat1a and facilitates its phosphorylation to enhance bcl2a expression; in mcm5 mutants, loss of the Mcm5-Stat1 complex decreases Stat1 phosphorylation and bcl2a transcription, accelerating apoptosis of immature T lymphocytes with genomic instability, revealing a replication-independent role for MCM5 in T cell survival via the Stat1-Bcl2 cascade. Co-immunoprecipitation (Mcm5-Stat1), phosphorylation assay, transcription analysis, mcm5 mutant zebrafish and mouse models Cell Death & Disease High 39929806
2021 MCM5 physically interacts with HDAC1; overexpression of both promotes EMT-dependent lung cancer progression, and astragaloside IV blocks the MCM5-HDAC1 interaction to inhibit cancer progression in vitro and in vivo. Co-immunoprecipitation, overexpression/knockdown, in vivo xenograft, drug competition assay Frontiers in Cell and Developmental Biology Medium 34409025
2025 MCM5 physically interacts with NRF2; downregulation of MCM5 (via AR/melatonin axis) reduces MCM5-NRF2 interaction, leading to uncontrolled NRF2/HMOX1 pathway activation, GPX4 suppression, and ferroptosis in prostate cancer cells. Co-immunoprecipitation (MCM5-NRF2), knockdown/overexpression, ferroptosis markers, in vivo tumor model Journal of Pineal Research Medium 41159313

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
2011 MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival. Cell death and differentiation 127 21233845
1999 Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F. Oncogene 127 10327050
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 66 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 m6 A-Dependent Modulation via IGF2BP3/MCM5/Notch Axis Promotes Partial EMT and LUAD Metastasis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 58 37171793
2023 Phase separation of DDX21 promotes colorectal cancer metastasis via MCM5-dependent EMT pathway. Oncogene 57 37029300
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 47 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 31 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 24 17565942
2021 MCM5 Aggravates the HDAC1-Mediated Malignant Progression of Lung Cancer. Frontiers in cell and developmental biology 23 34409025
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 22 35490917
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 16 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
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
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 14 32562513
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 1 39971831
2025 MCM5 UFMylation regulates replication origin firing and fork progression. The EMBO journal 1 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