Affinage

ORC6

Origin recognition complex subunit 6 · UniProt Q9Y5N6

Length
252 aa
Mass
28.1 kDa
Annotated
2026-06-10
42 papers in source corpus 23 papers cited in narrative 23 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

ORC6 encodes the smallest subunit of the origin recognition complex (ORC), an in vivo origin-binding complex first defined in budding yeast (PMID:8266075), and functions as a DNA-binding, helicase-loading subunit essential for the licensing of replication origins (PMID:18006685, PMID:21502537). Its middle domain adopts a TFIIB-like fold, and structural and mutagenesis studies of both the human protein and the Drosophila ortholog define Orc6 as a sequence-selective DNA-binding subunit of metazoan ORC that prefers poly(dA)/origin DNA and is required for replication in vitro and in cells (PMID:17283052, PMID:21502537, PMID:32986843). Orc6 anchors itself into the holocomplex through C-terminal contacts—to the Orc1-5 subcomplex in yeast and to a domain of Orc3 in metazoans, an interaction disrupted by a Meier-Gorlin syndrome mutation that impairs Orc6 incorporation and MCM2-7 loading (PMID:18006685, PMID:24137536). Mechanistically, Orc6 recruits Cdt1 through direct binding to enable iterative Mcm2-7 loading, and its N-terminal domain plus adjacent linker tethers ORC to Mcm2 during the binding-site switch that builds the MCM double hexamer; CDK phosphorylation of ORC inhibits this tethering, linking helicase loading to cell-cycle control (PMID:18006685, PMID:41055997). Re-licensing is further blocked by CDK phosphorylation of human Orc6 at Thr195 and by proteasome-dependent removal of Orc6 from chromatin at S-phase entry, which prevents aberrant MCM reloading and tetraploidy (PMID:38867464, PMID:40554748). In metazoans Orc6 carries a separable C-terminal cytokinesis function: it binds the septin Pnut/septin complex, stimulating septin GTPase activity and filament formation, and is required for furrow/midbody localization and abscission, such that domain deletion uncouples cytokinesis defects from intact DNA replication (PMID:12169736, PMID:12878722, PMID:18987337, PMID:25355953). Beyond core replication, human Orc6 localizes to the replication fork and acts as an accessory factor for mismatch repair by binding MutSα and promoting MutLα chromatin association, with ATR-dependent phosphorylation at Thr229 driving oxidative-damage checkpoint signaling (PMID:35622890, PMID:37096556). ORC6 also associates with nuclear p65 to support LPS-induced NFκB activation in macrophages (PMID:39143485).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1993 High

    Established that ORC6 is a bona fide subunit of an origin-binding complex, defining ORC as the in vivo recognition machinery for replication origins.

    Evidence One-hybrid screen and peptide sequencing of the purified 50 kDa yeast ORC subunit

    PMID:8266075

    Open questions at the time
    • Did not resolve Orc6's specific molecular contribution within ORC
    • No structural or DNA-contact information
  2. 2002 High

    Revealed that metazoan Orc6 has roles beyond replication, localizing to mitotic structures and being required for chromosome segregation and cytokinesis.

    Evidence Immunofluorescence, siRNA depletion and flow cytometry in human cells

    PMID:12169736

    Open questions at the time
    • Did not identify the molecular partners mediating the cytokinesis function
    • Did not separate replication from division defects
  3. 2003 High

    Mapped the cytokinesis function to a separable C-terminal domain that interacts with the septin Pnut, distinguishing it from the replication function.

    Evidence Two-hybrid, co-IP, deletion mutagenesis and dsRNA knockdown in Drosophila

    PMID:12878722

    Open questions at the time
    • Did not establish the biochemical effect of Orc6 on septins
    • Mammalian conservation of the septin interaction untested here
  4. 2004 High

    Showed Orc6 carries an RXL/Cy motif that docks S-phase cyclin Clb5, defining a mechanism by which Orc6 enforces a re-replication control switch rather than initiation.

    Evidence In vitro binding, Cy-motif mutagenesis, genetic epistasis and overreplication assays in yeast

    PMID:15105375

    Open questions at the time
    • Did not address whether metazoan Orc6 uses an analogous cyclin docking
    • Mechanism of overreplication suppression at origins not fully resolved
  5. 2007 High

    Identified Orc6 as a direct DNA-binding subunit, localizing origin recognition activity to its N-terminal core domain.

    Evidence In vitro DNA binding, reconstituted Drosophila ORC replication assay, mutagenesis and in vivo chromatin association

    PMID:17283052

    Open questions at the time
    • Structural basis of DNA recognition not defined here
    • Sequence specificity determinants only partially mapped
  6. 2007 High

    Defined Orc6 as the Cdt1-recruiting subunit required for iterative Mcm2-7 loading, mechanistically linking it to helicase loading.

    Evidence Reconstituted in vitro Mcm2-7 loading, direct binding, fusion complementation and yeast genetics

    PMID:18006685

    Open questions at the time
    • Did not visualize the structural transitions during loading
    • Did not establish how Orc6-Cdt1 cycling is regulated
  7. 2009 High

    Genetically separated the N-terminal replication function from the C-terminal mitotic function and demonstrated cross-species conservation of the replication role.

    Evidence P-element deletion, domain-mutant transgenic rescue and human-to-fly complementation in Drosophila

    PMID:19541634

    Open questions at the time
    • Did not define how the two domains are coordinated in vivo
    • Mitotic mechanism still unresolved at this stage
  8. 2011 High

    Provided a structural explanation for Orc6 DNA binding, showing its middle domain folds like the TFIIB helical domain.

    Evidence X-ray crystallography, mutagenesis and in vitro/cell-based replication assays for human Orc6

    PMID:21502537

    Open questions at the time
    • Structure of full-length Orc6 not solved here
    • DNA-bound complex structure not determined
  9. 2011 Medium

    Extended the metazoan pre-RC interaction map, implicating Orc6 contacts with Cdc6 and the chromatin chaperone HMGA1a in origin licensing and targeting.

    Evidence Co-IP, imaging, chromatin recruitment and domain-deletion analysis in human cells

    PMID:21461783

    Open questions at the time
    • Interactions shown by co-IP without reciprocal in vitro reconstitution
    • Functional contribution of HMGA1a-directed targeting not quantified
  10. 2011 High

    Used acute cell-cycle-stage-specific depletion to prove the cytokinesis/abscission role is direct and resides in the C-terminal 25 residues, separating it from replication-stress phenotypes.

    Evidence N-end rule degron, FRAP-based abscission assay and C-terminal deletion rescue in avian cells

    PMID:21422227

    Open questions at the time
    • Molecular effectors at the midbody not fully defined
    • Did not connect to septin biochemistry directly in this system
  11. 2008 High

    Demonstrated the biochemical consequence of the Orc6-septin interaction—stimulating septin GTPase activity and filament assembly.

    Evidence Septin purification, recombinant reconstitution, GTPase assay and electron microscopy of filaments

    PMID:18987337

    Open questions at the time
    • In vivo relevance of GTPase stimulation during cytokinesis not directly tested
    • Did not resolve binding stoichiometry
  12. 2013 High

    Placed Orc6 in the metazoan ORC architecture and tied a Meier-Gorlin syndrome mutation to defective Orc6-Orc3 assembly and MCM loading.

    Evidence 3D electron microscopy, biochemical binding, in vivo MCM loading and mutagenesis

    PMID:24137536

    Open questions at the time
    • High-resolution structure of the Orc6-Orc3 interface not obtained
    • Did not survey other disease alleles
  13. 2014 High

    Refined the cytokinesis mechanism by showing Orc6 dimerizes via TFIIB-like domains and bridges septins to promote filament formation.

    Evidence Recombinant septin reconstitution, in vitro filament assay and GTP-binding-domain mutagenesis in Drosophila

    PMID:25355953

    Open questions at the time
    • Did not determine the bridging structure at atomic resolution
    • Connection between dimerization and replication function unclear
  14. 2020 High

    Determined the full-length human Orc6 three-domain solution structure and localized a discrete DNA-binding domain confirming its origin-binding role.

    Evidence Solution NMR, mutagenesis and in vitro/cell-based replication assays

    PMID:32986843

    Open questions at the time
    • DNA-bound conformation not captured
    • Domain interplay within intact ORC not resolved
  15. 2017 Medium

    Established a developmental requirement for translational activation of maternal Orc6 mRNA for the first embryonic replication.

    Evidence CPE-targeted RNAi maternal mRNA ablation, Western blot and embryo replication assay in mouse

    PMID:20219456

    Open questions at the time
    • Translational control machinery only inferred from the CPE element
    • Single-system functional readout
  16. 2022 High

    Uncovered a non-replication chromatin role: Orc6 at the replication fork acts as an accessory factor for mismatch repair by binding MutSα and promoting MutLα loading.

    Evidence Co-IP, chromatin fractionation, fork localization and MMR/checkpoint assays in human cells

    PMID:35622890

    Open questions at the time
    • Structural basis of Orc6-MutSα binding undefined
    • Whether this is separable from origin licensing not fully resolved
  17. 2023 Medium

    Identified ATR-dependent Thr229 phosphorylation of Orc6 as the trigger for oxidative-damage checkpoint signaling and tumor suppression.

    Evidence Phospho-specific antibody, T229A mutagenesis, ATR signaling and tumorigenicity assays

    PMID:37096556

    Open questions at the time
    • Direct ATR-Orc6 kinase relationship inferred from dependency
    • Downstream effectors of phospho-Orc6 not fully mapped
  18. 2024 Medium

    Defined a CDK-dependent Thr195 phosphorylation that restrains re-licensing outside G1 and linked Orc6 to nucleolar function and ribosome biogenesis.

    Evidence T195E phosphomimetic mutagenesis, co-IP, cell cycle analysis and ribosome biogenesis assays

    PMID:38867464

    Open questions at the time
    • Phosphomimetic does not fully recapitulate endogenous phosphorylation
    • Mechanism connecting Orc6 to ribosome biogenesis unresolved
  19. 2024 Medium

    Implicated Orc6 in innate immune signaling through a p65 interaction required for LPS-induced NFκB activation.

    Evidence Co-IP, CRISPR knockout, shRNA silencing, cytokine and NFκB reporter assays with p65-epistasis in macrophages

    PMID:39143485

    Open questions at the time
    • Direct versus indirect Orc6-p65 binding not structurally defined
    • Relationship to Orc6 replication function unknown
  20. 2025 High

    Resolved how Orc6 enforces double-hexamer assembly by tethering ORC to Mcm2 during the binding-site switch, and how CDK phosphorylation disrupts this to inhibit loading.

    Evidence Single-molecule FRET, Orc6 linker mutagenesis, in vitro MCM loading and CDK phosphorylation assays

    PMID:41055997

    Open questions at the time
    • Precise CDK target residues on ORC controlling tethering not all defined
    • In vivo confirmation of the tethering intermediate pending
  21. 2025 Medium

    Showed proteasome-dependent removal of Orc6 from chromatin at S-phase entry is a safeguard against MCM reloading and tetraploidy.

    Evidence Chromatin fractionation, proteasome inhibition, MCM loading and ploidy analysis in human cells

    PMID:40554748

    Open questions at the time
    • Ubiquitin ligase mediating Orc6 turnover not identified
    • Direct evidence Orc6 is the proteasome substrate versus indirect effect not fully separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How Orc6's distinct activities—origin DNA binding, helicase loading, septin/cytokinesis, mismatch repair, checkpoint signaling, nucleolar/ribosome biogenesis and NFκB signaling—are spatially and temporally coordinated within a single small protein remains unresolved.
  • No unified model integrating replication and non-replication functions
  • Regulatory hierarchy among the multiple phosphorylation events undefined
  • Structure of Orc6 bound simultaneously to DNA and partner proteins lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005694 chromosome 2 GO:0005886 plasma membrane 2 GO:0005730 nucleolus 1
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-69306 DNA Replication 3 R-HSA-73894 DNA Repair 2
Partners
CDC6CDT1MCM2MUTSΑORC3PNUTRELA
Complex memberships
origin recognition complex (ORC)septin complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 ORC6 encodes the 50 kDa subunit of the yeast origin recognition complex (ORC) and interacts in vivo with yeast replication origins, establishing ORC as an in vivo origin-binding complex. One-hybrid screen; peptide sequencing of purified ORC subunit Science High 8266075
2000 Human ORC6 (hsORC6) does not co-immunoprecipitate stoichiometrically with ORC2-5 subunits, suggesting a more peripheral association with the human ORC holocomplex compared to yeast; it localizes to the nucleus along with other ORC subunits, and co-immunoprecipitates with a 65 kDa protein hyperphosphorylated in G1 and dephosphorylated in mitosis. Co-immunoprecipitation; cell fractionation; Western blot across cell cycle stages The Journal of Biological Chemistry Medium 10945994
2002 Human Orc6 localizes to kinetochores and a reticular-like structure at the cell periphery during mitosis, and to the midbody before cytokinesis; siRNA-mediated depletion causes multipolar spindles, aberrant mitosis, multinucleated cells, and decreased DNA replication, demonstrating essential roles in chromosome segregation and cytokinesis. Immunofluorescence microscopy; siRNA knockdown; flow cytometry Science High 12169736
2003 Drosophila Orc6 localizes to the cell membrane and cleavage furrow during cell division via its distinct C-terminal domain; this domain mediates interaction with the septin protein Pnut, as shown by two-hybrid and co-immunoprecipitation. Deletion of this C-terminal domain abolishes membrane/furrow localization and causes multinucleated cells without impairing DNA replication, demonstrating that cytokinesis and replication functions reside in separable domains. Two-hybrid screen; co-immunoprecipitation; immunofluorescence; dsRNA knockdown; deletion mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 12878722
2004 The S-phase cyclin Clb5 binds directly and stably to yeast ORC via an RXL/Cy motif in the Orc6 subunit, recognized by the hydrophobic patch of Clb5; this interaction is maintained from S phase through M phase and functions to prevent reinitiation at replicated origins (replication control switch), not for replication initiation per se. In vitro binding assay; site-directed mutagenesis of Cy motif; genetic epistasis; overreplication assay Genes & Development High 15105375
2006 In budding yeast, Orc6 is required for DNA replication entry into S phase after pre-RC formation; depletion in late G1 displaces Mcm2 and Mcm10 from chromatin and severely reduces replication origin firing. Orc6-YFP shows a punctate nuclear pattern consistent with subnuclear replication foci; no mitotic or cytokinetic function was detected in yeast. Conditional depletion; chromatin fractionation; live-cell imaging (YFP); DNA combing/BrdU incorporation The EMBO Journal High 17053779
2007 Drosophila Orc6 directly binds DNA—preferring poly(dA) sequences including replication origin fragments—via its N-terminal core replication domain (excluding the C-terminal domain); mutations in this domain abolish ORC DNA binding and DNA replication in vitro, and prevent chromosome association and cause dominant-negative effects in vivo. In vitro DNA binding assay; reconstituted Drosophila ORC replication assay; site-directed mutagenesis; chromatin immunoprecipitation/chromosome spreading in vivo Molecular and Cellular Biology High 17283052
2007 Yeast Orc6 recruits Cdt1 through two direct binding regions and its C-terminus (Orc6-CTD) anchors it to the Orc1-5 subcomplex; ORC lacking Orc6 fails to interact with Cdt1 or load Mcm2-7 onto origin DNA. A Cdt1–Orc6-CTD fusion rescues single-round but not multiple rounds of Mcm2-7 loading, demonstrating that dynamic Cdt1–Orc6 association is required for iterative helicase loading. In vitro Mcm2-7 loading assay; direct binding assay; reconstituted fusion protein complementation; yeast genetics Genes & Development High 18006685
2008 Drosophila Orc6 directly binds the septin complex (purified from embryos or reconstituted from recombinant proteins) via the coiled-coil domain of Pnut; Orc6 binding increases the intrinsic GTPase activity of the septin complex and, in the absence of GTP, enhances septin filament formation. Septin complex purification; recombinant reconstitution; GTPase activity assay; electron microscopy of filaments Molecular Biology of the Cell High 18987337
2009 In Drosophila, the N-terminal domain of Orc6 mediates the DNA replication function while the C-terminal domain is required for passage through M phase; deletion of C-terminal domain releases G1 arrest and restores DNA replication but causes mitotic accumulation. Human Orc6 rescues DNA replication in Drosophila orc6 deletion cells, demonstrating cross-species conservation of the replication function. P-element excision (orc6 deletion); transgenic rescue with deletion/point mutants; cell cycle analysis; cross-species complementation Proceedings of the National Academy of Sciences of the United States of America High 19541634
2011 The middle domain of human Orc6 adopts a fold homologous to the helical domain of transcription factor TFIIB; mutagenesis of residues identified by this structure abolishes DNA binding by Orc6 and reduces DNA replication in vitro and in cultured cells, defining Orc6 as a DNA-binding subunit of metazoan ORC. X-ray crystallography (structure determination); site-directed mutagenesis; in vitro DNA binding assay; in vitro replication assay; cell-based replication assay Proceedings of the National Academy of Sciences of the United States of America High 21502537
2011 Human Orc6 interacts with Cdc6 (co-immunoprecipitation); this interaction is required for licensing DNA replication (pre-RC formation). Orc6 also interacts with the chromatin chaperone HMGA1a via its acidic C-terminus and AT-hooks, potentially directing ORC to AT-rich heterochromatic origins. Co-immunoprecipitation; imaging; chromatin recruitment assay; domain-deletion analysis Cellular and Molecular Life Sciences Medium 21461783
2011 Using a temperature-sensitive N-end rule degron of avian Orc6, acute depletion specifically during mitosis (not S phase) causes asymmetric division and failure of cytokinesis with delayed daughter cell abscission; the C-terminal 25 residues of Orc6 are required for this function. S-phase depletion causes centrosome amplification that is suppressed by G2 checkpoint inhibition, indicating it is an indirect replication-stress consequence. N-end rule degron (temperature-sensitive degradation); fluorescence bleaching (FRAP-based abscission assay); C-terminal deletion mutant rescue The Journal of Cell Biology High 21422227
2013 Cryo-EM analysis shows metazoan ORC adopts a global architecture similar to budding yeast ORC. A Meier-Gorlin syndrome mutation in the conserved C-terminal helix of Orc6 impedes recruitment of Orc6 into the ORC hexamer; biochemical studies show this C-terminal region of Orc6 binds a previously uncharacterized domain of Orc3, and this interaction is required for ORC function and MCM2-7 loading in vivo. 3D electron microscopy; bioinformatic structural analysis; biochemical binding assay; in vivo MCM loading assay; site-directed mutagenesis eLife High 24137536
2014 Drosophila Orc6 forms dimers through interactions of its N-terminal TFIIB-like domains and directly binds the septin complex to facilitate septin filament formation; Orc6 acts as a molecular bridge stimulating septin polymerization. GTP-binding/hydrolysis by Pnut, Sep1, and Sep2, and intact C-terminal domains of septins, are required for complex integrity. Recombinant septin complex reconstitution; in vitro filament formation assay; mutagenesis of GTP-binding domains; biochemical binding assay Molecular Biology of the Cell High 25355953
2017 Recruitment of ORC6L (Orc6) from a dormant maternal mRNA via a CPE element in its 3' UTR during mouse oocyte maturation is required for DNA replication in 1-cell embryos; RNAi ablation of the maternal Orc6l mRNA prevents the maturation-associated increase in ORC6L protein and blocks DNA replication after fertilization. RNAi-mediated maternal mRNA ablation; Western blot; DNA replication assay in embryos Developmental Biology Medium 20219456
2020 Solution NMR structure of full-length human Orc6 reveals three independent domains (N, M, C); a DNA-binding domain (HsOrc6-DBD) within these domains is identified; mutagenesis of key residues abolishes DNA binding and reduces DNA replication, confirming Orc6 as a DNA-binding subunit of human ORC. Solution NMR; mutagenesis; in vitro DNA binding assay; cell-based DNA replication assay Nucleic Acids Research High 32986843
2022 Human Orc6 localizes to the replication fork during S phase and functions as an accessory factor for the mismatch repair (MMR) complex; Orc6 directly binds MutSα and enhances chromatin association of MutLα; without Orc6, MMR complex assembly and checkpoint signaling in response to oxidative DNA damage are abrogated. Co-immunoprecipitation (Orc6–MutSα); chromatin fractionation (MutLα association); replication fork localization (iPOND or equivalent); MMR activity assay; checkpoint signaling assay Proceedings of the National Academy of Sciences of the United States of America High 35622890
2023 Human Orc6 is phosphorylated at Thr229 predominantly during S phase in response to oxidative stress; this ATR-dependent phosphorylation is required for DNA damage checkpoint signaling (ATR signaling), fork progression halting, and efficient repair to prevent tumorigenesis. Phospho-dead Orc6 increases tumorigenicity. Phospho-specific antibody; site-directed mutagenesis (T229A phospho-dead); ATR signaling assay; cell proliferation/tumorigenicity assay Molecular and Cellular Biology Medium 37096556
2024 CDK-dependent phosphorylation of human Orc6 at Thr195 occurs during mitosis; the phosphomimetic T195E mutant impedes S-phase progression. Phosphorylated Orc6 associates more robustly with ORC outside G1, suggesting phospho-Orc6 prevents licensing activity of Orc1-5 outside G1. Orc6 and phospho-Orc6 localize to nucleolar organizing centers and regulate ribosome biogenesis. Site-directed mutagenesis (T195E phosphomimetic); co-immunoprecipitation; cell cycle analysis; nucleolar localization (immunofluorescence); ribosome biogenesis assay Molecular and Cellular Biology Medium 38867464
2025 During ORC binding-site switching in replication origin licensing, the N-terminal half of Orc6 (folded Orc6N domain plus adjacent unstructured linker) tethers ORC to the N-terminal region of Mcm2, preventing ORC release into solution; this tethering precedes ORC release from initial Mcm2-7 binding and is required for efficient double-hexamer formation. CDK phosphorylation of ORC inhibits this Orc6-Mcm2 tethering interaction, providing a mechanism for CDK inhibition of MCM loading. Single-molecule FRET assay; mutagenesis of Orc6 linker; in vitro MCM loading assay; CDK phosphorylation assay Proceedings of the National Academy of Sciences of the United States of America High 41055997
2025 Human Orc6 dissociates from chromatin upon S-phase entry in a proteasome-dependent manner; inhibition of the proteasome causes accumulation of chromatin-bound Orc6, which promotes aberrant MCM loading after S-phase entry, ultimately leading to tetraploid cell formation. Chromatin fractionation; proteasome inhibitor treatment; MCM loading assay; cell cycle/ploidy analysis (flow cytometry) Journal of Cell Science Medium 40554748
2024 ORC6 associates with nuclear p65 after LPS stimulation; this interaction is necessary for NFκB activation in macrophages. ORC6 silencing or knockout inhibits LPS-induced NFκB activation and pro-inflammatory cytokine production, while ORC6 overexpression enhances these responses and cannot rescue the response when p65 is silenced. Co-immunoprecipitation (ORC6–p65); CRISPR/Cas9 knockout; shRNA silencing; cytokine ELISA; NFκB reporter assay; in vivo macrophage-specific knockdown Cell Communication and Signaling Medium 39143485

Source papers

Stage 0 corpus · 42 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Isolation of ORC6, a component of the yeast origin recognition complex by a one-hybrid system. Science (New York, N.Y.) 352 8266075
2002 Orc6 involved in DNA replication, chromosome segregation, and cytokinesis. Science (New York, N.Y.) 189 12169736
2004 Interaction of the S-phase cyclin Clb5 with an "RXL" docking sequence in the initiator protein Orc6 provides an origin-localized replication control switch. Genes & development 119 15105375
2007 Orc6 is required for dynamic recruitment of Cdt1 during repeated Mcm2-7 loading. Genes & development 116 18006685
2003 A cytokinetic function of Drosophila ORC6 protein resides in a domain distinct from its replication activity. Proceedings of the National Academy of Sciences of the United States of America 96 12878722
2000 Identification and characterization of the human ORC6 homolog. The Journal of biological chemistry 69 10945994
2007 Role of the Orc6 protein in origin recognition complex-dependent DNA binding and replication in Drosophila melanogaster. Molecular and cellular biology 57 17283052
2006 An essential role for Orc6 in DNA replication through maintenance of pre-replicative complexes. The EMBO journal 57 17053779
2013 A Meier-Gorlin syndrome mutation in a conserved C-terminal helix of Orc6 impedes origin recognition complex formation. eLife 50 24137536
2011 Structural analysis of human Orc6 protein reveals a homology with transcription factor TFIIB. Proceedings of the National Academy of Sciences of the United States of America 48 21502537
2009 Functional analysis of an Orc6 mutant in Drosophila. Proceedings of the National Academy of Sciences of the United States of America 41 19541634
2008 Drosophila Orc6 facilitates GTPase activity and filament formation of the septin complex. Molecular biology of the cell 37 18987337
2008 Reduction of Orc6 expression sensitizes human colon cancer cells to 5-fluorouracil and cisplatin. PloS one 37 19112505
2011 Different roles of the human Orc6 protein in the replication initiation process. Cellular and molecular life sciences : CMLS 23 21461783
2020 Structural basis of DNA replication origin recognition by human Orc6 protein binding with DNA. Nucleic acids research 22 32986843
2011 A vertebrate N-end rule degron reveals that Orc6 is required in mitosis for daughter cell abscission. The Journal of cell biology 22 21422227
2021 ORC6, Negatively Regulated by miR-1-3p, Promotes Proliferation, Migration, and Invasion of Hepatocellular Carcinoma Cells. Frontiers in cell and developmental biology 21 34395415
2010 Recruitment of Orc6l, a dormant maternal mRNA in mouse oocytes, is essential for DNA replication in 1-cell embryos. Developmental biology 21 20219456
2014 Functional insight into the role of Orc6 in septin complex filament formation in Drosophila. Molecular biology of the cell 20 25355953
2022 Orc6 is a component of the replication fork and enables efficient mismatch repair. Proceedings of the National Academy of Sciences of the United States of America 18 35622890
2022 ORC6 acts as a biomarker and reflects poor outcome in clear cell renal cell carcinoma. Journal of Cancer 15 35711825
2015 Drosophila model of Meier-Gorlin syndrome based on the mutation in a conserved C-Terminal domain of Orc6. American journal of medical genetics. Part A 13 26139588
2015 Further insight into the phenotype associated with a mutation in the ORC6 gene, causing Meier-Gorlin syndrome 3. American journal of medical genetics. Part A 12 25691413
2024 Origin recognition complex subunit 6 (ORC6) is a key mediator of LPS-induced NFκB activation and the pro-inflammatory response. Cell communication and signaling : CCS 7 39143485
2020 Humanized Drosophila Model of the Meier-Gorlin Syndrome Reveals Conserved and Divergent Features of the Orc6 Protein. Genetics 7 33037049
2017 [A boy with Meier-Gorlin syndrome carrying a novel ORC6 mutation and uniparental disomy of chromosome 16]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 6 28186598
2024 Long Non-coding RNA COX10-AS1 Promotes Glioma Progression by Competitively Binding miR-1-3p to Regulate ORC6 Expression. Neuroscience 5 38244670
2024 A miR-361-5p/ ORC6/ PLK1 axis regulates prostate cancer progression. Experimental cell research 5 38885805
2023 DNA Damage-Induced, S-Phase Specific Phosphorylation of Orc6 is Critical for the Maintenance of Genome Stability. Molecular and cellular biology 5 37096556
2022 Meier-Gorlin Syndrome: Clinical Misdiagnosis, Genetic Testing and Functional Analysis of ORC6 Mutations and the Development of a Prenatal Test. International journal of molecular sciences 5 36012502
2025 An Orc6 tether mediates ORC binding-site switching during replication origin licensing. Proceedings of the National Academy of Sciences of the United States of America 3 41055997
2025 Curcumol overcomes cisplatin resistance and rewires glycolysis-H3K9la-ORC6 axis to trigger ferroptosis in bladder cancer. Chinese journal of cancer research = Chung-kuo yen cheng yen chiu 3 41523832
2024 Phosphorylation of Orc6 During Mitosis Regulates DNA Replication and Ribosome Biogenesis. Molecular and cellular biology 3 38867464
2025 METTL3/IGF2BP3 mediates ORC6 via N6-methyladenosine modification to promote the progression of pancreatic ductal adenocarcinoma. Gene 2 40185346
2025 An Orc6 tether mediates ORC binding site switching during replication origin licensing. bioRxiv : the preprint server for biology 1 40462942
2025 Proteasome-dependent Orc6 removal from chromatin upon S-phase entry safeguards against minichromosome maintenance complex reloading and tetraploidy. Journal of cell science 1 40554748
2014 Evidence of positive selection at codon sites localized in the C-terminal peptide of ORC6. Biotechnology letters 1 24122247
2026 Machine learning derived ORC6 as a hub biomarker for predicting tumor microenvironment, prognoses, and therapeutic responses in lung adenocarcinoma. Translational oncology 0 41875810
2026 Novel Insights into the Oncogenic Role and Clinical Significance of ORC6L in Breast Cancer. Breast cancer (Dove Medical Press) 0 42039914
2026 TRPS1 inhibits cervical cancer progression by suppressing ORC6-mediated tumor stemness. Tissue & cell 0 42247779
2025 Unexpected molecular mechanism of Orc6-based Meier-Gorlin syndrome: insights from a humanized Drosophila model. Genetics 0 40986665
2023 [Genetic analysis of a child with Meier-Gorlin syndrome due to a variant of ORC6 gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 37730234

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