| 1999 |
The ATP binding activity of MCM6 within the MCM4-MCM6-MCM7 complex is critical for DNA helicase activity; mutating conserved ATPase motifs of MCM6 abolishes helicase activity while MCM4 plays a role in single-stranded DNA binding. The helicase and ssDNA binding activities of the complex can be separated. |
In vitro helicase assay with ATPase motif mutagenesis of recombinant mouse MCM4/6/7 expressed in insect cells |
Molecular and cellular biology |
High |
10567526
|
| 1999 |
MCM5 and MCM6 gene expression is regulated by the transcription factor E2F through multiple E2F binding sites in their promoters; E2F sites in the MCM6 promoter (including a novel E2F-like sequence) are required for serum-stimulated transcriptional induction. |
Promoter-reporter assays with E2F site mutations, serum stimulation, and forced E2F1 expression in REF52 cells |
Oncogene |
High |
10327050
|
| 2002 |
Mouse Cdt1 directly interacts with MCM6 via the C-terminal region of Cdt1 (amino acids 407–477); geminin associates with the central region of Cdt1 (amino acids 177–380) and inhibits both Cdt1-MCM6 interaction and Cdt1 DNA binding activity. |
Yeast two-hybrid analysis, bacterial expression and purification, domain mapping |
The Journal of biological chemistry |
High |
12192004
|
| 1999 |
Fission yeast Mcm6 (SpMcm6p/Mis5) associates with chromosomal replication origins specifically during G1 and S phases, colocalizing with ORC at a ~1 kb region of ars2004 and ars3002, indicating it is loaded onto origins to initiate replication. |
Chromatin immunoprecipitation, immunostaining of spread nuclei, cell-cycle fractionation |
Molecular and cellular biology |
High |
10490657
|
| 1997 |
Human MCM6 protein undergoes cell-cycle-dependent subcellular redistribution; it exists in two forms (NP-40 extractable and nucleus-bound) and associates in vivo with MCM2 and MCM7 as a heteromeric complex. |
Co-immunoprecipitation, subcellular fractionation, cell cycle synchronization experiments |
Genes to cells : devoted to molecular & cellular mechanisms |
Medium |
9286856
|
| 1998 |
Human MCM6 protein associates with chromatin in a multiprotein complex containing other Mcm proteins; chromatin-bound MCM6 is released by micrococcal nuclease digestion, and some MCM6 also occurs as a monomer on chromatin. |
Micrococcal nuclease digestion of chromatin, fractionation, antibody-based detection |
The Journal of biological chemistry |
Medium |
9516426
|
| 2006 |
Phosphorylation of MCM4 at Thr-19 and Thr-110 by CDK2/cyclin A or EBV protein kinase inactivates MCM4-MCM6-MCM7 complex-associated DNA helicase activity; EBV-PK can also phosphorylate MCM6 itself to further inhibit helicase activity. |
In vitro helicase assay, site-directed mutagenesis of MCM4 N-terminal residues, kinase assay with CDK2/cyclin A and EBV-PK |
Journal of virology |
High |
17005684
|
| 2009 |
Saccharomyces cerevisiae Mcm6 directly binds the checkpoint mediator Mrc1 through its 168-amino-acid C-terminal region; this interaction is required for replication checkpoint activation in response to methyl methanesulfonate (MMS) but not hydroxyurea. Physical fusion of Mcm6 mutant with Mrc1 suppresses the checkpoint defect. |
Protein interaction mapping, two amino acid substitution mutants abolishing Mrc1 binding, in vivo checkpoint assays, genetic suppression by fusion protein |
Molecular and cellular biology |
High |
19620285
|
| 2010 |
The Mcm6/2 and Mcm5/3 ATPase active sites (Walker B box and arginine finger motifs) contribute to the function of the putative Mcm2/5 'gate' in the Mcm2-7 ring; mutational analysis shows these sites modulate overall helicase activity differentially. |
Walker B and arginine finger mutagenesis in S. cerevisiae Mcm2-7, ATPase and helicase functional assays |
Nucleic acids research |
High |
20484375
|
| 2010 |
Chromatin-bound MCM6 exists in two distinct states in G1 phase (low and high levels); cells with high chromatin-bound MCM6 are in late G1 past the restriction point and cycle with committed phases (S, G2, M), linking MCM6 loading level to cell cycle commitment. |
Multivariate flow cytometry measuring chromatin-bound Mcm6, PCNA, DNA content, and mitotic marker; serum starvation/release and stathmokinetic experiments |
BMC cell biology |
Medium |
20398392
|
| 2021 |
BLM helicase directly and physically interacts with MCM6: BLM binds the N-terminal domain of Mcm6 in G1 and switches to the C-terminal Cdt1-binding domain of Mcm6 in S-phase. Disruption of BLM/Mcm6 interaction leads to supra-normal DNA replication speed and delays repair of replication-dependent DSBs, establishing BLM as a negative regulator of replication speed via Mcm6. |
Co-IP of BLM complex components, domain-specific binding site mapping, replication speed assays, DNA damage sensitivity assays upon BLM-Mcm6 interaction disruption |
Nucleic acids research |
High |
34370039
|
| 2022 |
YAP-TEAD complex binds the MCM6 promoter to induce MCM6 transcription in gastric cancer; MCM6 in turn activates PI3K/Akt/GSK3β signaling to support YAP-potentiated tumorigenicity. MCM6 deficiency blocks ATR/Chk1-mediated DNA damage response. |
ChIP-PCR, luciferase reporter assays, RNA-seq, knockdown/overexpression in vitro and xenograft mouse models, patient-derived organoids |
Theranostics |
High |
36185598
|
| 2010 |
NMR chemical shift assignments define the Cdt1-binding domain (CBD) of human MCM6 as having a winged-helix fold; the CBD directly interacts with Cdt1 and likely mediates chromatin loading of the MCM2-7 complex. |
Triple-resonance NMR spectroscopy for backbone chemical shift assignments of human MCM6 CBD |
Biomolecular NMR assignments |
Medium |
20623209
|
| 2024 |
Avermectin B1a occupies the CDT1-binding domain (CBD) of MCM6 (hydrogen bond contacts at Glu763, Ile760, Arg771, Glu774) and blocks the MCM6-CDT1 interaction, thereby inhibiting DNA replication licensing, causing G0/G1 arrest and apoptosis; upregulation of MCM6 or CDT1 reverses these effects. |
Molecular docking, ELISA-based binding assay, cell cycle analysis, rescue experiments with MCM6/CDT1 overexpression |
Environmental pollution |
Medium |
39579921
|
| 2024 |
SIRT7-mediated lysine crotonylation of MCM6 at K599 (MCM6-K599cr) is upregulated in response to DNA replication stress, primarily due to disassembly of the MCM2-7 complex; this modification is regulated by RNF8-mediated ubiquitination. |
Mass spectrometry-based PTM identification, western blot for Kcr, RNF8 knockdown/overexpression, SIRT7 manipulation, ubiquitination assay |
Cell proliferation |
Medium |
39477811
|
| 2024 |
RNF125 interacts with MCM6 and mediates its ubiquitination; RNF125 promotes HCC cell proliferation mainly through MCM6, establishing RNF125 as an E3 ubiquitin ligase regulating MCM6 protein homeostasis. |
Pull-down, co-immunoprecipitation, ubiquitination assay, co-transfection rescue experiments |
Oncology letters |
Medium |
38298426
|
| 2023 |
MCM6 promotes intrahepatic cholangiocarcinoma progression by upregulating E2F1, which in turn mediates epithelial-mesenchymal transition (EMT); E2F1 knockdown partially blocks the pro-malignant effects of MCM6 overexpression. |
GSEA, MCM6 knockdown/overexpression, E2F1 knockdown epistasis experiments, in vitro and in vivo models |
Carcinogenesis |
Medium |
37185675
|
| 2023 |
De novo MCM6 missense variant p.(Cys158Tyr) affecting a zinc-binding cysteine in the MCM6 zinc finger domain (essential for MCM complex dimerization and helicase activity induction) causes defects in ciliogenesis and cell proliferation in patient-derived fibroblasts. |
Trio exome/genome sequencing, patient fibroblast functional assays for ciliogenesis and cell proliferation |
Human genetics |
Medium |
37198333
|
| 2021 |
LINC00472 recruits DNA methyltransferases to the MCM6 promoter to induce site-specific DNA methylation and reduce MCM6 expression; restoration of MCM6 weakens the tumor-suppressive effect of LINC00472, establishing epigenetic silencing of MCM6 by LINC00472 as a mechanism suppressing TNBC metastasis via MEK/ERK pathway. |
LINC00472 overexpression, MCM6 rescue experiments, DNA methylation assay at MCM6 promoter, in vitro and in vivo tumor models |
Aging |
Medium |
33668040
|
| 2023 |
MCM6 expression in keratinocytes is governed by the IL-22/STAT3 pathway; benvitimod inhibits p-JAK1/p-JAK2 to restrain STAT3 activation and thereby reduces MCM6 expression, suppressing keratinocyte proliferation in psoriasis. |
MCM6 knockdown, IL-22/STAT3 pathway inhibition, JAK inhibitor experiments, in vitro HaCaT cells and in vivo IMQ-induced mouse model |
Journal of dermatological science |
Medium |
36774328
|
| 2023 |
UBE3A (E6AP ubiquitin ligase) interacts with MCM6 (and MCM2/4), identified by yeast two-hybrid; E6AP knockout enhances ubiquitination of MCM2/4/6 but E6AP is not their E3 ligase. MCM6 and E6AP synergistically regulate proliferation and migration of lung adenocarcinoma cells. |
Yeast two-hybrid, co-immunoprecipitation, ubiquitination assay, combined knockdown proliferation/migration assays, xenograft mouse model |
FEBS open bio |
Medium |
37454373
|
| 2025 |
MCM6 knockdown reduces nuclear c-Myc levels and promotes its ubiquitin-mediated degradation; c-Myc as a transcription factor binds the MCM6 promoter and promotes MCM6 transcription, forming a positive feedback loop that drives cisplatin resistance via enhanced DNA damage repair. |
MCM6 knockdown, western blot for c-Myc, ubiquitination assay, c-Myc ChIP at MCM6 promoter, cisplatin sensitivity assays in vitro and in vivo |
International journal of biological macromolecules |
Medium |
39805445
|