Affinage

MCM8

DNA helicase MCM8 · UniProt Q9UJA3

Length
840 aa
Mass
93.7 kDa
Annotated
2026-06-10
61 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MCM8 is an AAA+ ATPase/helicase that, together with its obligate partner MCM9, forms a hexameric DNA helicase central to homologous recombination repair of stalled or collapsed replication forks and DNA interstrand crosslinks (PMID:22771120, PMID:22771115, PMID:37535404). MCM8 possesses intrinsic DNA helicase and ATPase activities and is recruited to chromatin at the elongation phase of replication, where it supports normal fork progression and the recruitment of replication factors (PMID:15707891, PMID:36042199). MCM8 and MCM9 mutually stabilize each other and are rapidly recruited to DNA damage sites, where they promote MRN-dependent end resection, generation of ssDNA/RPA, and downstream RAD51-mediated strand invasion and recombination-associated DNA synthesis (PMID:22771120, PMID:23401855, PMID:26215093, PMID:32528060). This activity makes MCM8-9 an alternative replicative helicase capable of restarting stalled forks through an HR pathway operating downstream of RAD51 (PMID:28487407). The accessory factor HROB (MCM8IP/C17orf53) directly binds the MCM8-9 heterodimer and stimulates its helicase activity by driving conformational rearrangement of the heterohexamer, acting downstream of complex loading on ssDNA (PMID:32528060, PMID:38678026, PMID:37535404). Structurally, MCM8 and MCM9 assemble as a 3:3 heterohexamer with a central DNA-binding channel, and DNA binding triggers rotation between the N-terminal DNA-binding and C-terminal AAA+ ATPase tiers that reorganizes DNA-binding loops to enable unwinding (PMID:34043945, PMID:37535404). These functions are essential for primordial germ cell development, meiotic recombination, ovarian reserve preservation, and genome stability: MCM8-deficient mice are sterile with meiotic prophase I arrest, MCM8 facilitates repair synthesis and recombination intermediate formation during meiosis, and helicase activity is specifically required for HR-driven PGC development (PMID:22771120, PMID:16189551, PMID:42085144, PMID:41959065). MCM8 additionally promotes pre-replication complex assembly through interactions with CDC6 and ORC2 (PMID:15684404), resolves R-loops by retaining the RNA helicases DDX5 and DHX9 (PMID:38858601), and in non-nuclear contexts mediates mitophagy following nitric-oxide-triggered TRIM21 ubiquitination that disrupts the MCM9 interaction and drives cytosolic relocalization (PMID:39195969).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2005 High

    Establishing whether MCM8 is itself an active helicase and where it acts in DNA replication was the foundational question; the answer distinguished it from the canonical MCM2-7 licensing helicase.

    Evidence In vitro helicase/ATPase assays with recombinant protein plus depletion/reconstitution and chromatin fractionation in Xenopus egg extract

    PMID:15707891

    Open questions at the time
    • Did not define the in vivo functional partner of MCM8
    • Elongation role described without identifying the recombination context later established
  2. 2005 Medium

    Whether MCM8 acts before origin firing was tested, showing it contributes to pre-replication complex assembly distinct from its elongation role.

    Evidence RNAi knockdown, chromatin fractionation, and co-immunoprecipitation with CDC6 and ORC2 in human cells

    PMID:15684404

    Open questions at the time
    • Reconciliation with the later HR-centric model of MCM8 function is unclear
    • Direct mechanism of CDC6/ORC2 engagement not resolved
  3. 2005 High

    Genetic analysis in Drosophila placed the MCM8 ortholog within meiotic recombination, defining it as a factor promoting crossover-associated repair synthesis downstream of RAD51 but upstream of resolution.

    Evidence Genetic epistasis and quantification of crossovers/gene conversion in Drosophila rec mutants

    PMID:16189551

    Open questions at the time
    • Biochemical activity underlying the recombination role not addressed in this system
    • Mammalian generality untested at the time
  4. 2012 High

    Identifying MCM9 as the obligate MCM8 partner unified the field: the MCM8-9 complex was shown to drive HR and to be essential for fertility.

    Evidence Knockout mice, co-immunoprecipitation, HR assays, RAD51/RPA foci, and DT40 ICL-sensitivity/SCE assays with FA/BRCA2 epistasis

    PMID:22771115 PMID:22771120

    Open questions at the time
    • Precise step within HR (resection vs. synthesis) not yet pinpointed
    • Mechanism of recruitment to damage sites unknown
  5. 2013 High

    Recruitment dynamics were clarified: MCM8-9 forms a heterodimer that is rapidly recruited to damage sites, promotes RAD51 loading, and associates with chromatin at late replication stages.

    Evidence Reciprocal Co-IP, HR-GFP reporter, ChIP at damage sites, and Xenopus egg extract fractionation

    PMID:23401855 PMID:23518502

    Open questions at the time
    • Did not identify the recruitment factor
    • Relationship to origin licensing left as a negative (no Cdt1 interaction)
  6. 2015 High

    The HR step requiring MCM8-9 was defined as resection: the complex interacts with MRN and is required for its nuclease activity and stable DSB association to generate ssDNA.

    Evidence Co-IP, nuclease assays, ATPase-motif mutagenesis, and RPA/ssDNA generation assays

    PMID:26215093

    Open questions at the time
    • How ATPase activity mechanistically enables MRN nuclease function unresolved
    • Whether resection and later synthesis roles are separable not addressed
  7. 2017 High

    Whether MCM8-9 can substitute for the replicative helicase was tested, establishing it as an alternative helicase that restarts stalled forks via an HR pathway downstream of RAD51.

    Evidence Auxin-inducible MCM2 degron, EdU incorporation, and epistasis with MCM8/9 KO and RAD51 inhibition

    PMID:28487407

    Open questions at the time
    • Extent of genome-wide reliance on this pathway unquantified
    • Structural basis of helicase activity not yet known
  8. 2019 High

    The long-sought recruitment factor was identified as HROB, which brings MCM8-9 to damage sites for recombination-associated synthesis and acts redundantly with HELQ.

    Evidence Hrob knockout mice with prophase I arrest, epistasis with HELQ, HR assays, and damage-site recruitment

    PMID:31467087

    Open questions at the time
    • Whether HROB only recruits or also activates the helicase was unresolved here
    • Molecular interface with MCM8-9 not mapped
  9. 2020 High

    HROB was shown to directly stimulate MCM8-9 helicase activity and to bridge the complex to RPA, defining it as an activator rather than a mere tether.

    Evidence Co-IP, in vitro helicase stimulation assay, HR-GFP reporter, and DNA fiber assay

    PMID:32528060

    Open questions at the time
    • Conformational mechanism of stimulation not yet structurally defined
    • Contribution to long-tract vs short-tract conversion only partly resolved
  10. 2020 Medium

    Additional regulators and roles emerged: HORMAD1 restricts MCM8-9 nuclear localization affecting mismatch repair, broadening the regulatory context of the complex.

    Evidence Co-IP, subcellular fractionation, MLH1 ChIP, and MMR reporter assay

    PMID:32647118

    Open questions at the time
    • Direct vs indirect effect on MMR not fully separated
    • Physiological setting beyond cancer cells unclear
  11. 2021 High

    Structural questions about the helicase architecture began to be answered: MCM8 and MCM9 form a 3:3 heterohexamer with a DNA-binding channel, and the MCM8 winged-helix domain binds DNA.

    Evidence X-ray crystallography of WHD and NTDs combined with a low-resolution cryo-EM map and DNA binding assays

    PMID:32295713 PMID:34043945

    Open questions at the time
    • DNA-engaged active conformation not resolved at this stage
    • Mechanism of unwinding unmodeled
  12. 2022 High

    The fork-protective dimension was established: beyond restart, MCM8-9 aids normal fork progression and directs BRCA1/RAD51 to protect nascent strands from degradation.

    Evidence DNA fiber assay, iPOND, and RAD51/BRCA1 foci in MCM8/9 knockout cells

    PMID:36042199

    Open questions at the time
    • How helicase activity links to fork protection mechanistically unresolved
    • Separation from the resection role not addressed
  13. 2023 High

    Cryo-EM in multiple states revealed the activation mechanism: HROB converts N-tier ring symmetry and rotary motion between N- and C-tier rings drives unwinding.

    Evidence Cryo-EM single-particle analysis with biochemical unwinding assays

    PMID:37535404

    Open questions at the time
    • Full DNA-bound activated state with ATP analogs not yet captured here
    • Order of loading, ring formation, and activation not fully sequenced
  14. 2024 High

    Biochemical dissection separated complex assembly from catalysis: a stable interface forms the obligate heterodimer while a labile interface mediates hexamer assembly and contributes disproportionately to unwinding, with HROB acting after loading.

    Evidence Reconstituted in vitro and single-molecule helicase assays, ATPase assays, interaction mapping, and structural modeling

    PMID:38678026

    Open questions at the time
    • In vivo regulation of the labile interface unknown
    • How asymmetry maps to specific repair steps unresolved
  15. 2024 High

    A replication-independent genome-maintenance role was uncovered: MCM8 retains DDX5/DHX9 at R-loops, and POI-causative mutants with weakened DDX5 binding accumulate R-loops.

    Evidence Co-IP, S9.6 R-loop immunofluorescence, proximity ligation, and MCM8 knockout mouse PGC analysis

    PMID:38858601

    Open questions at the time
    • Whether helicase activity is required for R-loop resolution not separated
    • Relationship to canonical HR role unclear
  16. 2026 High

    Genetic dissection of catalysis in vivo showed helicase activity is essential for mitotic HR, PGC development, and ovarian reserve but dispensable for meiotic recombination, and the two ATPase sites are functionally asymmetric yet both essential.

    Evidence Walker B helicase-deficient knock-in mice, PGC counting, HR assays, and ovarian reserve assessment

    PMID:42085144

    Open questions at the time
    • Mechanism of the meiotic-vs-mitotic functional split not explained
    • Non-helicase meiotic function not molecularly defined
  17. 2023 Medium

    A non-nuclear function was reported: nitric-oxide-induced TRIM21 ubiquitination disrupts MCM8-MCM9 binding, exports MCM8 to mitochondria, and triggers LIR-mediated mitophagy that limits cGAS-STING activation.

    Evidence Co-IP, ubiquitination assay, fractionation, mitophagy/LC3 colocalization, cGAS-STING reporter, and MCM8 KO Kawasaki disease mouse model

    PMID:39195969

    Open questions at the time
    • How a replication/HR helicase acquires a mitophagy receptor role is unexplained
    • Single lab without independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how MCM8-9 helicase catalysis is mechanistically partitioned across its multiple roles—resection support, fork restart, fork protection, R-loop resolution, and the helicase-independent meiotic function—and how the cytoplasmic mitophagy role integrates with its canonical nuclear biology.
  • No unified model links helicase activity to each distinct repair outcome
  • Switch between nuclear HR and cytoplasmic mitophagy roles not mechanistically defined
  • Low-confidence cancer interactions (NR4A1/E2F1, CDC42) lack independent validation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 4 GO:0140657 ATP-dependent activity 4 GO:0140097 catalytic activity, acting on DNA 3 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 3 GO:0005739 mitochondrion 1 GO:0005829 cytosol 1
Pathway
R-HSA-73894 DNA Repair 5 R-HSA-1474165 Reproduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-69306 DNA Replication 3 R-HSA-9612973 Autophagy 1
Partners
CDC6DDX5DHX9HROBMCM9MRE11ORC2RPA1
Complex memberships
MCM8-MCM9 helicase heterohexamer

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Recombinant MCM8 displays both DNA helicase and ATPase activities in vitro. MCM8 does not associate with the soluble MCM2-7 complex but binds chromatin upon initiation of DNA synthesis. MCM8 depletion slows DNA synthesis and reduces chromatin recruitment of RPA34 and DNA polymerase-alpha. ATP binding in MCM8 is required to rescue DNA synthesis in MCM8-depleted Xenopus egg extracts, indicating MCM8 functions in the elongation step of DNA replication. In vitro helicase/ATPase assays with recombinant protein; Xenopus egg extract depletion/reconstitution; chromatin fractionation; colocalization with replication foci Cell High 15707891
2005 MCM8 co-immunoprecipitates with MCM4, MCM6, and MCM7 from HeLa cells, suggesting MCM8 interacts with the MCM4-6-7 helicase complex. Co-immunoprecipitation from HeLa cell lysates Nucleic acids research Low 12771218
2005 Human MCM8 (hMCM8) accumulates on chromatin during early G1 phase before the MCM2-7 complex. hMCM8 interacts in vivo with hCDC6 and hORC2. Depletion of hMCM8 by RNAi delays entry into S phase and reduces chromatin loading of hCDC6 and the hMCM2-7 complex, indicating hMCM8 is required for pre-replication complex assembly. RNAi knockdown; chromatin fractionation; co-immunoprecipitation; cell cycle analysis Molecular and cellular biology Medium 15684404
2005 Drosophila REC (MCM8 ortholog) is required for most meiotic crossing over. Epistasis experiments place REC after the RAD51 ortholog SPN-A but before the endonuclease MEI-9. In rec mutants, crossovers are reduced ~95% while noncrossover gene conversion frequency increases and gene conversion tract lengths are reduced ~50%, consistent with a role for REC in facilitating repair synthesis during meiotic recombination. Genetic epistasis analysis; quantification of crossovers and gene conversion in Drosophila mutants PLoS genetics High 16189551
2008 Chromatin immunoprecipitation shows MCM8 colocalizes with MCM7 and CDC6 at the c-MYC replication initiation zone during mid-G1; MCM8 also colocalizes with chromatin-bound CDK2. Immunogold electron microscopy shows MCM8 and MCM7 differ in spatial relation to RPA70 during S phase. Chromatin immunoprecipitation; immunogold electron microscopy Microscopy research and technique Medium 18072282
2012 MCM8 and MCM9 form a protein complex and coregulate each other's stability. Loss of MCM8 or MCM9 impairs chromatin recruitment of HR factors RAD51 and RPA, strongly reduces HR efficiency, and prevents cells from overcoming transient replication fork inhibition. MCM8-/- mice are sterile: spermatocytes are blocked in meiotic prophase I and females develop only arrested primary follicles and frequently develop ovarian tumors. Knockout mice; co-immunoprecipitation; HR assay; immunofluorescence for Rad51/RPA foci; chromosomal damage assays in embryonic fibroblasts Molecular cell High 22771120
2012 MCM8 and MCM9 form a complex required for HR repair induced by DNA interstrand crosslinks (ICLs). Chicken DT40 cells lacking MCM8 or MCM9 are highly sensitive to ICL-inducing agents. During ICL repair, MCM8 and MCM9 form nuclear foci that partly colocalize with RAD51. MCM8-9 works downstream of the FA and BRCA2/RAD51 pathways and is required for HR that promotes sister chromatid exchanges, likely as a hexameric ATPase/helicase. Gene knockout in chicken DT40 cells; immunofluorescence foci; sister chromatid exchange assays; genetic epistasis with FA and BRCA2 pathways Molecular cell High 22771115
2013 MCM8 and MCM9 physically associate with each other in mammalian cells, and MCM8 is required for the stability of MCM9 protein. Depletion of MCM8 or MCM9 reduces HR repair efficiency and sensitizes cells to cisplatin. Chromatin immunoprecipitation using DR-GFP cells and Xenopus egg extract demonstrated that MCM8 and MCM9 are rapidly recruited to DNA damage sites and promote RAD51 recruitment. Co-immunoprecipitation; siRNA knockdown; HR-GFP reporter assay; ChIP at DNA damage sites; Xenopus egg extract Molecular and cellular biology High 23401855
2013 In Xenopus egg extract, MCM8 and MCM9 form a dimeric (heterodimeric) complex that associates with chromatin at later stages of DNA replication; this association is stimulated by DNA damage. MCM9 is not essential for loading of MCM2-7 onto chromatin during origin licensing, and no interaction with Cdt1 was detected. Xenopus egg extract fractionation; chromatin binding assays; co-immunoprecipitation Cell cycle Medium 23518502
2015 MCM8-9 complex is required for DNA resection by MRN (MRE11-RAD50-NBS1) at DSBs to generate ssDNA. MCM8-9 interacts with MRN and is required for the nuclease activity and stable association of MRN with DSBs. The ATPase motifs of MCM8-9 are required for recruitment of MRE11 to DNA damage foci. Co-immunoprecipitation; nuclease assays; ATPase motif mutagenesis; immunofluorescence foci; RPA/ssDNA generation assays Nature communications High 26215093
2017 Upon acute depletion of the MCM2-7 replicative helicase subunit MCM2, cells maintain residual DNA synthesis that requires the MCM8-9 complex. This MCM8-9-dependent synthesis operates via a homologous recombination pathway downstream from RAD51 and is promoted by DSB induction, identifying MCM8-9 as an alternative replicative helicase for restarting stalled forks in S phase. Auxin-inducible degron system for MCM2 depletion; EdU incorporation; genetic epistasis with MCM8/9 KO; RAD51 inhibition Genes & development High 28487407
2019 HROB (C17orf53) recruits the MCM8-9 helicase to sites of DNA damage to promote recombination-associated DNA synthesis. The HROB-MCM8-MCM9 pathway acts redundantly with the HELQ helicase; cells lacking both HROB and HELQ have severely impaired HR. Mice with targeted Hrob mutations are infertile with prophase I meiotic arrest, phenocopying MCM8/9 deficiency. Genetic knockout mice; epistasis with HELQ; HR assays; recruitment of MCM8-9 to damage foci; genetic interaction Genes & development High 31467087
2020 MCM8IP (C17orf53/HROB) directly associates with MCM8-9 and RPA1, and stimulates the helicase activity of the MCM8-9 complex in vitro. MCM8IP-deficient cells exhibit HR defects (especially in long-tract gene conversion) downstream of RAD51 loading. The interactions of MCM8IP with MCM8-9 and RPA facilitate HR and promote replication fork progression. Co-immunoprecipitation; in vitro helicase stimulation assay; HR-GFP reporter assay; DNA fiber assay Nature communications High 32528060
2020 HORMAD1 interacts with the MCM8-MCM9 complex and prevents its efficient nuclear localization. HORMAD1-expressing cancer cells consequently show reduced MLH1 chromatin binding and DNA mismatch repair defects. Co-immunoprecipitation; subcellular fractionation; immunofluorescence; MLH1 ChIP; MMR reporter assay Cell death & disease Medium 32647118
2021 Crystal structure of the winged-helix domain (WHD) of human MCM8 at 1.21 Å resolution reveals a conserved winged-helix architecture; structure analysis and biochemical study identified DNA-binding ability and crucial residues of MCM8-WHD. X-ray crystallography; DNA binding assay Biochemical and biophysical research communications Medium 32295713
2021 Crystal structures of the N-terminal domains (NTDs) of MCM8 and MCM9, combined with a 6.6 Å cryo-EM map, show the MCM8/9 complex forms a 3:3 heterohexamer in alternating subunit arrangement with a positively charged DNA binding channel and a putative ssDNA exit pathway. Zinc-finger motifs can bind iron as well. X-ray crystallography; cryo-electron microscopy Structure High 34043945
2022 MCM8/9 helicase function aids normal replication fork progression; upon persistent stalling, MCM8/9 directs BRCA1 and RAD51 to protect forks from excessive nascent strand degradation. Loss of MCM8 or MCM9 slows overall replication rate and allows excessive nascent strand degradation. DNA fiber assay; iPOND; RAD51/BRCA1 foci; MCM8/9 knockout cells Nature communications High 36042199
2023 Cryo-EM structures of the MCM8/9 complex reveal it forms a heterohexamer through threefold symmetry with a central DNA-accommodating channel; OB-domain hairpins protrude into the channel for duplex unwinding. HROB activation converts the N-tier ring from C3 to C1 symmetry with conformational change at the trimer interface, and flexible C-tier ring rotary motion relative to the N-tier ring is required for unwinding activity. Cryo-EM single particle analysis; biochemical DNA unwinding assays eLife High 37535404
2024 HROB makes important yet transient contacts with both MCM8 and MCM9, binding the MCM8-9 heterodimer with highest affinity. MCM8-9 unwinds DNA as a hexamer that assembles from dimers on DNA in an ATP-dependent manner. Two distinct protein-protein interfaces exist: a stable interface forming the obligate heterodimer (across which HROB binds) and a labile interface mediating hexamer assembly. The ATPase site at the labile interface contributes disproportionately more to DNA unwinding. HROB promotes DNA unwinding downstream of MCM8-9 loading and ring formation on ssDNA. Biochemical interaction mapping; in vitro helicase assay; single-molecule DNA unwinding; ATPase assays; cryo-EM/structural modeling Nature communications High 38678026
2024 MCM8 interacts with RNA helicases DDX5 and DHX9; loss of MCM8 reduces retention of DDX5 and DHX9 at R-loops, causing R-loop accumulation and genome instability. POI-causative MCM8 mutants with decreased interaction with DDX5 display increased R-loop levels. MCM8 deficiency in mice causes proliferation defects in primordial germ cells (PGCs) and impaired fertility. Co-immunoprecipitation; R-loop immunofluorescence (S9.6 antibody); proximity ligation assay; mouse knockout model; PGC counting The EMBO journal High 38858601
2023 MCM8 regulates E2F1 expression by interacting with the transcription factor NR4A1, thereby affecting E2F1 transcriptional activity. MCM8 and E2F1 collaboratively influence aerobic glycolysis in renal cell carcinoma cells. Co-immunoprecipitation; reporter assay; knockdown/overexpression with metabolic readouts Cell biology and toxicology Low 39992472
2023 MCM8 promotes colorectal cancer progression by interacting with CDC42 and competitively inhibiting HRD1-mediated ubiquitination and degradation of CDC42, thereby stabilizing CDC42 protein and promoting cell cycle G1-to-S transition. Co-immunoprecipitation; ubiquitination assay; overexpression/knockdown; cell cycle analysis; xenograft model Journal of translational medicine Low 41546027
2023 MCM8 is regulated by nitric oxide signaling: NO promotes TRIM21-mediated ubiquitination of MCM8, disrupting its interaction with MCM9 and promoting cytosolic export of MCM8. In the cytosol, MCM8 relocates to mitochondrial pore-forming proteins, promotes their ubiquitination by TRIM21, and recruits LC3 via an LIR motif to initiate mitophagy. This suppresses mitochondrial DNA-mediated type I interferon activation via cGAS-STING. MCM8-deficient mice develop more severe coronary artery vasculopathy in a Kawasaki disease model. Co-immunoprecipitation; ubiquitination assay; subcellular fractionation; mitophagy assay (LC3 co-localization); cGAS-STING reporter; mouse KO model Nature cardiovascular research Medium 39195969
2025 FANCD2 is essential for the recruitment of MCM8/9 to ICL damage-induced nuclear foci, but acts independently of FANCD2 monoubiquitination. MCM8/9 and FANCD2 interact via the MCM8/9 core domain (by Co-IP). Combined loss of MCM9 and FANCD2 does not cause additive DNA damage, indicating an epistatic relationship within the same ICL repair pathway. Co-immunoprecipitation; immunofluorescence foci; genetic epistasis (double KO); γH2AX and cell survival assays DNA repair Medium 41237481
2026 Cryo-EM structures of MCM8/9 with DNA, HROB, and ATP analogs show that DNA binding induces a pronounced rotational rearrangement between the N-terminal DNA binding and C-terminal AAA+ ATPase domains, reorganizing DNA-binding loops into a staircase configuration. HROB associates with both halves of the heterohexamer and drives a similar rotation prior to DNA binding, providing a unified mechanistic model for MCM8/9 helicase activation by HROB. Cryo-electron microscopy; biochemical DNA binding and unwinding assays bioRxivpreprint Medium 42094346
2026 In MCM8-deficient mouse spermatocytes, DSBs accumulate and are resected normally, but downstream recombination intermediates (D-loops/joint molecules) barely form and MutSgamma foci do not form efficiently. MCM8 binds D-loop structures in vitro. MCM8 also participates in regulating meiotic DSB number. This places MCM8 function at post-resection recombination intermediate formation/stability during meiosis. Cytological analysis of spermatocytes; genomic DSB mapping (SPO11-oligo sequencing); in vitro D-loop binding assay; MCM8 KO mice bioRxivpreprint Medium 41959065
2026 MCM8-9 helicase activity (AAA+ ATPase function) is essential for ovarian reserve preservation and POI prevention, specifically required for mitotic HR and primordial germ cell development, but dispensable for meiotic recombination. The two distinct ATPase active sites of MCM8-9 exhibit functional asymmetry yet both are equally essential for HR, PGC development, and ovarian reserve. Helicase-deficient mouse knock-in models (Walker B motif mutations); PGC counting; HR assays; ovarian reserve assessment PNAS High 42085144
2005 E2F1 transcription factor directly binds to the MCM8 promoter (demonstrated by ChIP) and transcriptionally activates MCM8. MCM8 is regulated by E2F1-4 but not E2F5-8. NF-Y binding motif accompanies the E2F motif in mammalian MCM8 promoters. Chromatin immunoprecipitation (ChIP); promoter reporter assays; E2F1 overexpression Gene Medium 16325355

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 MCM8- and MCM9-deficient mice reveal gametogenesis defects and genome instability due to impaired homologous recombination. Molecular cell 178 22771120
2014 Exome sequencing reveals MCM8 mutation underlies ovarian failure and chromosomal instability. The Journal of clinical investigation 166 25437880
2012 Mcm8 and Mcm9 form a complex that functions in homologous recombination repair induced by DNA interstrand crosslinks. Molecular cell 126 22771115
2005 MCM8 is an MCM2-7-related protein that functions as a DNA helicase during replication elongation and not initiation. Cell 116 15707891
2013 The MCM8-MCM9 complex promotes RAD51 recruitment at DNA damage sites to facilitate homologous recombination. Molecular and cellular biology 114 23401855
2015 Minichromosome maintenance complex component 8 (MCM8) gene mutations result in primary gonadal failure. Journal of medical genetics 94 25873734
2017 MCM8 and MCM9 Nucleotide Variants in Women With Primary Ovarian Insufficiency. The Journal of clinical endocrinology and metabolism 90 27802094
2015 MCM8-9 complex promotes resection of double-strand break ends by MRE11-RAD50-NBS1 complex. Nature communications 88 26215093
2005 REC, Drosophila MCM8, drives formation of meiotic crossovers. PLoS genetics 83 16189551
2019 Control of homologous recombination by the HROB-MCM8-MCM9 pathway. Genes & development 66 31467087
2003 A new member of the MCM protein family encoded by the human MCM8 gene, located contrapodal to GCD10 at chromosome band 20p12.3-13. Nucleic acids research 57 12771218
2017 New MCM8 mutation associated with premature ovarian insufficiency and chromosomal instability in a highly consanguineous Tunisian family. Fertility and sterility 56 28863940
2005 Involvement of human MCM8 in prereplication complex assembly by recruiting hcdc6 to chromatin. Molecular and cellular biology 53 15684404
2017 Acute inactivation of the replicative helicase in human cells triggers MCM8-9-dependent DNA synthesis. Genes & development 52 28487407
2019 The MCM8/9 complex: A recent recruit to the roster of helicases involved in genome maintenance. DNA repair 48 30743181
2020 MCM8IP activates the MCM8-9 helicase to promote DNA synthesis and homologous recombination upon DNA damage. Nature communications 47 32528060
2020 Aberrantly expressed HORMAD1 disrupts nuclear localization of MCM8-MCM9 complex and compromises DNA mismatch repair in cancer cells. Cell death & disease 40 32647118
2019 Inhibiting the MCM8-9 complex selectively sensitizes cancer cells to cisplatin and olaparib. Cancer science 35 30648820
2019 MCM8- and MCM9 Deficiencies Cause Lifelong Increased Hematopoietic DNA Damage Driving p53-Dependent Myeloid Tumors. Cell reports 31 31509747
2020 Novel loss-of-function mutation in MCM8 causes premature ovarian insufficiency. Molecular genetics & genomic medicine 30 32048466
2020 A Novel Phenotype Combining Primary Ovarian Insufficiency Growth Retardation and Pilomatricomas With MCM8 Mutation. The Journal of clinical endocrinology and metabolism 29 32242235
2020 Germline biallelic Mcm8 variants are associated with early-onset Lynch-like syndrome. JCI insight 27 32841224
2013 Mcm8 and Mcm9 form a dimeric complex in Xenopus laevis egg extract that is not essential for DNA replication initiation. Cell cycle (Georgetown, Tex.) 26 23518502
2021 MCM8 is regulated by EGFR signaling and promotes the growth of glioma stem cells through its interaction with DNA-replication-initiating factors. Oncogene 24 34131285
2022 A multi-functional role for the MCM8/9 helicase complex in maintaining fork integrity during replication stress. Nature communications 22 36042199
2024 MCM8 interacts with DDX5 to promote R-loop resolution. The EMBO journal 20 38858601
2008 Colocalization of MCM8 and MCM7 with proteins involved in distinct aspects of DNA replication. Microscopy research and technique 20 18072282
2023 Molecular functions of MCM8 and MCM9 and their associated pathologies. iScience 19 37378315
2021 Knockdown of MCM8 inhibits development and progression of bladder cancer in vitro and in vivo. Cancer cell international 17 33931059
2020 Two novel mutations in the MCM8 gene shared by two Chinese siblings with primary ovarian insufficiency and short stature. Molecular genetics & genomic medicine 17 32652893
2021 Downregulation of MCM8 expression restrains the malignant progression of cholangiocarcinoma. Oncology reports 15 34523691
2023 MCM8-mediated mitophagy protects vascular health in response to nitric oxide signaling in a mouse model of Kawasaki disease. Nature cardiovascular research 14 39195969
2024 Mechanism of DNA unwinding by MCM8-9 in complex with HROB. Nature communications 13 38678026
2021 Knockdown of MCM8 functions as a strategy to inhibit the development and progression of osteosarcoma through regulating CTGF. Cell death & disease 13 33828075
2020 4-Aminobiphenyl inhibits the DNA homologous recombination repair in human liver cells: The role of miR-630 in downregulating RAD18 and MCM8. Toxicology 12 32433928
2021 Structural study of the N-terminal domain of human MCM8/9 complex. Structure (London, England : 1993) 11 34043945
2023 Function and mechanism of MCM8 in the development and progression of colorectal cancer. Journal of translational medicine 10 37710286
2023 Structural and mechanistic insights into the MCM8/9 helicase complex. eLife 9 37535404
2024 A novel cancer-germline gene DAZL promotes progression and cisplatin resistance of non-small cell lung cancer by upregulating JAK2 and MCM8. Gene 6 38588931
2020 Crystal structure of the winged-helix domain of MCM8. Biochemical and biophysical research communications 4 32295713
2005 Comparative genomics on MCM8 orthologous genes reveals the transcriptional regulation by transcription factor E2F. Gene 4 16325355
2025 Expression patterns of MCM8 in lung adenocarcinoma and its correlation with key biological processes. European journal of medical research 3 40033404
2025 AmNA-Modified Antisense Oligonucleotide Targeting MCM8 as a Cancer-Specific Chemosensitizer for Platinum Compounds. Cancer science 3 40098305
2023 Enhancer-driven transcription of MCM8 by E2F4 promotes ATR pathway activation and glioma stem cell characteristics. Hereditas 3 37349788
2025 The potential of MCM8 as a biomarker in esophageal carcinoma: a comprehensive analysis integrating m6a methylation and angiogenesis. European journal of medical research 2 40346692
2025 MCM8 promotes NR4A1-mediated E2F1 transcription and facilitates renal cell carcinoma through enhancing aerobic glycolysis. Cell biology and toxicology 1 39992472
2025 A novel homozygous frameshift mutation in MCM8 causes primary gonadal dysgenesis in both genders. Journal of assisted reproduction and genetics 1 40064807
2025 Clinical syndromes linked to biallelic germline variants in MCM8 and MCM9. HGG advances 1 40684266
2025 MCM8/9 and FANCD2 interact within a shared pathway in response to replication stress caused by DNA crosslinks. DNA repair 1 41237481
2024 MCM8 promotes lung cancer progression through upregulating DNAJC10. Journal of cellular and molecular medicine 1 39031896
2023 Mechanism of DNA unwinding by hexameric MCM8-9 in complex with HROB. Research square 1 37461676
2021 Associations of MCM8 rs3761873 and rs16991617 variants with abnormal uterine bleeding induced by copper intrauterine device. The journal of obstetrics and gynaecology research 1 34889489
2026 MCM8 promotes colorectal cancer progression by competitively inhibiting HRD1-mediated CDC42 ubiquitination and degradation. Journal of translational medicine 0 41546027
2026 EBNA1BP2 (EBP2) promotes the progression of hepatocellular carcinoma through upregulating the expression of MCM8 and HMGB1. Cell death & disease 0 41935051
2026 Critical roles of MCM8 in meiotic recombination during mouse spermatogenesis. bioRxiv : the preprint server for biology 0 41959065
2026 MCM8-9 helicase activity protects primordial germ cell development to prevent premature ovarian insufficiency. Proceedings of the National Academy of Sciences of the United States of America 0 42085144
2026 Structural Activation of DNA Unwinding by MCM8/9/HROB. bioRxiv : the preprint server for biology 0 42094346
2025 EP300 Modulates MCM8 Transcription and Augments the Malignant Phenotype of Hepatitis B Virus-Positive Hepatocellular Carcinoma Cells. The Kaohsiung journal of medical sciences 0 40095759
2024 Understanding the novel MCM8 gene mutation: primary ovarian insufficiency and uterine hypoplasia in siblings. BMJ case reports 0 39074937
2024 Investigation of an MCM8 gene variant in women with premature ovarian insufficiency. Einstein (Sao Paulo, Brazil) 0 39607112
2023 Mechanism of DNA unwinding by hexameric MCM8-9 in complex with HROB. bioRxiv : the preprint server for biology 0 37398313

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