Affinage

SETMAR

Histone-lysine N-methyltransferase SETMAR · UniProt Q53H47

Length
684 aa
Mass
78.0 kDa
Annotated
2026-04-28
45 papers in source corpus 26 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SETMAR (Metnase) is a primate-specific SET-transposase fusion protein that functions at the intersection of DNA double-strand break repair, replication fork restart, chromosome decatenation, and transcriptional regulation. Its SET domain dimethylates H3K36, which promotes euchromatization and recruitment of NHEJ factors such as Ku70/Ku80 to DSBs, while its transposase-derived DDN-motif endonuclease domain cleaves ssDNA overhangs to process broken ends for ligation in concert with DNA Ligase IV and hPso4 (PMID:16332963, PMID:21491884, PMID:32458986, PMID:18773976). SETMAR also enhances Topoisomerase IIα-mediated decatenation and supercoil relaxation—regulated by automethylation at K485—and facilitates stalled replication fork restart by loading Exo1 onto ssDNA gaps in a manner controlled by Chk1 phosphorylation at S495, which differentially promotes DSB repair while restraining fork restart (PMID:18790802, PMID:27974460, PMID:22231448). Beyond repair, SETMAR binds ~5,000 Hsmar1 TIR remnants genome-wide and uses its methyltransferase activity to regulate expression and alternative splicing of hundreds of genes, including methylation of the non-histone substrate snRNP70 at K130 and H3K36 at the SMARCA2 promoter to drive thyroid differentiation gene expression (PMID:35378129, PMID:25795785, PMID:38900084).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2005 High

    The initial identification of SETMAR as an H3K4/K36 methyltransferase that promotes NHEJ and foreign DNA integration established its dual enzymatic identity and primary repair function.

    Evidence In vitro methyltransferase assays, IR survival, and plasmid integration in human cells

    PMID:16332963

    Open questions at the time
    • Catalytic residues and domain contributions not yet dissected
    • Mechanism by which histone methylation promotes NHEJ unknown
    • Whether transposase domain contributes to repair not tested
  2. 2006 High

    Demonstrating that the transposase domain retains site-specific TIR DNA binding, 5'-end cleavage, and integration activities—but is defective for 3'-end cleavage—defined the residual enzymatic repertoire inherited from Hsmar1.

    Evidence In vitro transposase activity, DNA binding, and transposition assays

    PMID:17130240 PMID:17403897

    Open questions at the time
    • Physiological substrates of transposase domain cleavage in repair not identified
    • Whether TIR binding is relevant to DSB repair unclear
  3. 2007 High

    Mutagenesis of R432 (HTH motif) and D483 (DDE-like motif) demonstrated that sequence-specific TIR DNA binding and catalytic cleavage are separable activities, resolving how a single domain can be recruited and act enzymatically through independent determinants.

    Evidence Site-directed mutagenesis with in vitro DNA binding and cleavage assays

    PMID:17877369

    Open questions at the time
    • Whether these residues are required for NHEJ function in vivo not yet tested
    • Structure of the transposase domain not yet solved
  4. 2008 High

    Identification of hPso4 as the factor that recruits SETMAR to DSBs (redirecting it from TIR to non-TIR sites) and of DNA Ligase IV as a direct interactor explained how SETMAR integrates into the NHEJ pathway, while the TopoIIα interaction and automethylation-regulated decatenation enhancement revealed a second major cellular function in chromosome segregation.

    Evidence Reciprocal co-IP, co-localization after IR, siRNA knockdown with NHEJ assay, in vitro kDNA decatenation with purified proteins, automethylation at K485

    PMID:18263876 PMID:18773976 PMID:18790802

    Open questions at the time
    • Structural basis of hPso4–SETMAR interaction unknown
    • Whether automethylation occurs in vivo at endogenous levels not confirmed
    • How H3K36me2 deposition at DSBs cooperates with end processing unclear
  5. 2010 High

    Discovery that SETMAR interacts with PCNA and RAD9 and is required for stalled replication fork restart expanded its roles beyond DSB repair to replication stress, while structural determination of the dimeric transposase catalytic domain showed that dimerization (disrupted by F460K) is essential for DNA binding, cleavage, and NHEJ.

    Evidence Co-IP, DNA fiber assay, HU-induced stress, X-ray crystallography at 2.37 Å, dimerization mutant analysis

    PMID:20416268 PMID:20457750 PMID:20521842

    Open questions at the time
    • How PCNA/RAD9 interaction coordinates with SETMAR enzymatic activities unresolved
    • No full-length SETMAR structure available
  6. 2011 High

    Characterization of SETMAR's endonuclease activity on ssDNA overhangs—and the requirement of the D483 catalytic residue for end-joining stimulation—established that nucleolytic processing of DNA ends is a direct enzymatic contribution to NHEJ, not just a vestigial transposase activity.

    Evidence In vitro endonuclease assay with purified protein, cell-extract NHEJ reconstitution with catalytic mutant

    PMID:21491884

    Open questions at the time
    • Substrate specificity versus Artemis at modified DNA ends not fully delineated
    • Contribution relative to other end-processing nucleases in vivo unknown
  7. 2012 High

    Identification of Chk1 phosphorylation at S495 as a regulatory switch that promotes DSB chromatin association while inhibiting fork restart provided the first post-translational mechanism explaining how SETMAR's dual repair functions are differentially controlled.

    Evidence In vivo phosphorylation mapping, S495A mutagenesis, DSB repair and fork restart assays

    PMID:22231448

    Open questions at the time
    • Whether S495 phosphorylation status changes during the cell cycle not examined
    • Downstream signaling consequences of phosphorylation not fully mapped
  8. 2012 High

    Demonstrating that the DDN catalytic motif (N610) is specifically required for ssDNA binding and cleavage of fork substrates—and that restoring the ancestral DDE motif paradoxically impairs these activities—revealed that evolutionary divergence of the active site adapted SETMAR for genome maintenance rather than transposition.

    Evidence DDN-to-DDD/DDE mutagenesis, in vitro fork substrate cleavage, in vivo NHEJ and fork restart assays

    PMID:24573677

    Open questions at the time
    • No co-crystal structure of DDN active site with ssDNA substrate
    • Whether other DDN-containing transposase-derived proteins share this adaptation unknown
  9. 2015 High

    Discovery of snRNP70-K130 as a non-histone methylation substrate and the finding that the SET domain (independent of H3K36me2) is required for ssDNA overhang cleavage broadened the functional scope of SETMAR's methyltransferase activity beyond chromatin modification.

    Evidence SILAC-based proteomics, in vitro methyltransferase assay, SET domain deletion mutant with HU restart assay

    PMID:25795785 PMID:26437079

    Open questions at the time
    • Functional consequence of snRNP70-K130 methylation on splicing not demonstrated
    • Whether SET domain allosterically regulates transposase domain structurally unknown
  10. 2016 High

    Showing that SETMAR loads Exo1 onto ssDNA at stalled forks via its DNA-binding (not cleavage) activity provided a mechanistic explanation for how SETMAR facilitates 5'-strand resection during fork restart.

    Evidence Co-IP, in vitro Exo1 loading assay with stalled fork substrates, domain mutant analysis

    PMID:27974460

    Open questions at the time
    • Whether Exo1 loading requires prior SETMAR dimerization not tested
    • In vivo reconstitution of the SETMAR-Exo1 axis at individual forks not achieved
  11. 2019 Medium

    Genome-wide ChIP showing SETMAR targets Hsmar1 TIR remnants and methylase-dependent transcriptomic changes affecting ~1500 genes established that SETMAR functions as a domesticated transposase-derived transcriptional regulator.

    Evidence ChIP, RNA-seq, methylase-deficient mutant comparison in human cells

    PMID:30329085

    Open questions at the time
    • Direct versus indirect transcriptional targets not distinguished
    • Whether H3K36me2 is the sole mediator of transcriptional effects unclear
  12. 2020 High

    Linking SETMAR upregulation to radiation resistance in glioblastoma through H3K36me2-dependent Ku80 recruitment to DSBs provided in vivo disease-relevant validation that SETMAR's chromatin-modifying activity is the critical upstream event enabling NHEJ factor retention at break sites.

    Evidence SETMAR KD, H3K36A mutant, Ku80 ChIP at DSBs, orthotopic mouse model

    PMID:32458986

    Open questions at the time
    • Whether SETMAR inhibition is therapeutically viable without impairing normal NHEJ unknown
    • Contribution of transposase nuclease activity to radio-resistance not assessed
  13. 2022 High

    The crystal structure of the SETMAR DBD–TIR complex and CRISPR KO transcriptomics together revealed how dimeric TIR recognition at ~5000 genomic sites governs expression and alternative splicing of neuronal and splicing-factor genes, linking structural biology to genome-wide regulatory function.

    Evidence X-ray crystallography (2.37 Å), ChIP-seq, CRISPR KO with RNA-seq and splicing analysis

    PMID:35378129

    Open questions at the time
    • No full-length SETMAR structure showing SET–transposase domain communication
    • Mechanism by which TIR binding regulates alternative splicing not defined
  14. 2024 Medium

    Demonstration that SETMAR methylates H3K36 at the SMARCA2 promoter to drive chromatin remodeling and thyroid differentiation gene expression, with SETMAR itself regulated by METTL3-mediated m6A modification, placed SETMAR in an epitranscriptomic–epigenomic regulatory circuit controlling cell differentiation.

    Evidence ChIP, ATAC-seq, methyltransferase assay, m6A-seq, loss-of-function and rescue in thyroid cells

    PMID:38900084

    Open questions at the time
    • Whether this axis operates in non-thyroid tissues unknown
    • Direct structural evidence for SETMAR at SMARCA2 promoter lacking
  15. 2026 Medium

    Identification of O-GlcNAcylation of NONO at S147 as a signal that stabilizes NONO–SFPQ interaction and promotes the full-length SETMAR isoform—linking metabolic sensing through protein glycosylation to NHEJ competence via H3K36me2 and Ku70 recruitment—added a new upstream regulatory layer controlling SETMAR splicing and function.

    Evidence O-GlcNAc site mutagenesis, co-IP, splicing assay, H3K36me2 ChIP, Ku70 recruitment, IR survival in vitro and in vivo

    PMID:41535889

    Open questions at the time
    • Whether O-GlcNAc regulation operates in non-cancer contexts unknown
    • Functional differences between SETMAR-L and SETMAR-S beyond NHEJ not systematically examined
    • Single-lab finding awaiting independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length SETMAR structure revealing inter-domain communication between SET and transposase domains, the precise mechanism by which H3K36me2 promotes NHEJ factor retention at chromatin, and the physiological significance of SETMAR-mediated alternative splicing regulation remain unresolved.
  • No full-length structure showing SET–transposase interdomain architecture
  • Mechanism coupling H3K36me2 deposition to Ku70/Ku80 chromatin retention not biochemically defined
  • In vivo contribution of SETMAR nuclease versus methyltransferase to repair not genetically separated in animal models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 5 GO:0003677 DNA binding 4 GO:0140096 catalytic activity, acting on a protein 3 GO:0042393 histone binding 2
Localization
GO:0005634 nucleus 5 GO:0005694 chromosome 2
Pathway
R-HSA-73894 DNA Repair 6 R-HSA-4839726 Chromatin organization 3 R-HSA-69306 DNA Replication 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953854 Metabolism of RNA 2
Partners
CHEK1EXO1LIG4PCNAPRPF19RAD9ASNRNP70TOP2A
Complex memberships
SETMAR–TopoIIα complexhPso4–SETMAR complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 SETMAR (Metnase) methylates histone H3 lysines 4 and 36 via its SET domain, promotes nonhomologous end-joining (NHEJ) repair of DNA double-strand breaks, and enhances integration of exogenous DNA into host cell genomes. In vitro methyltransferase assay, ionizing radiation survival assays, plasmid integration assays in human cells Proceedings of the National Academy of Sciences of the United States of America High 16332963
2006 The transposase domain of SETMAR retains Hsmar1 transposase activities including site-specific DNA binding to transposon ends (TIR), paired-ends complex assembly, 5'-end cleavage in Mn2+, and integration at TA dinucleotide target sites, but has a severe defect for 3'-end cleavage, limiting complete transposition. In vitro transposase activity assays, DNA binding assays, transposition assays with engineered Hsmar1 transposon Molecular and cellular biology High 17130240
2007 SETMAR binds Hsmar1 inverted-repeat (TIR) sequences and introduces single-strand nicks into these sequences in vitro; DNA repair following SETMAR-mediated cleavage predominantly follows a homology-dependent pathway in vivo, distinct from the NHEJ-dominant repair after full transposase (Hsmar1-Ra) cleavage. In vitro DNA binding and nicking assays; in vivo repair pathway analysis in human cells Molecular and cellular biology High 17403897
2007 The R432 residue within the helix-turn-helix (HTH) motif is critical for SETMAR's sequence-specific TIR DNA binding (R432A abolishes TIR binding); the DDE-like motif residue D483 is essential for DNA cleavage activity (D483A abolishes cleavage); DNA cleavage activity is uncoupled from TIR-specific binding. Site-directed mutagenesis, in vitro DNA binding and cleavage assays Biochemistry High 17877369
2008 SETMAR physically interacts and co-localizes with Topoisomerase IIα (TopoIIα); purified SETMAR greatly enhances TopoIIα-mediated decatenation of kinetoplast DNA; SETMAR automethylates at K485, and automethylation represses enhancement of TopoIIα decatenation activity. Co-immunoprecipitation, co-localization, in vitro kDNA decatenation assay with purified proteins, neutralizing antisera, automethylation assay Nucleic acids research High 18790802
2008 Human Pso4 (hPso4) forms a stable complex with SETMAR on both TIR and non-TIR DNA; hPso4 is required to bring SETMAR to DSB sites after ionizing radiation and is necessary for SETMAR-mediated stimulation of DNA end joining and genomic integration. Co-immunoprecipitation, co-localization after ionizing radiation, siRNA knockdown with functional NHEJ assay The Journal of biological chemistry High 18263876
2008 SETMAR interacts with DNA Ligase IV, a key NHEJ component; SETMAR assists in joining all types of free DNA ends equally, prevents long deletions during end processing, and improves NHEJ accuracy; SETMAR has little effect on homologous recombination repair. Co-immunoprecipitation, plasmid-based NHEJ assay, γ-H2AX kinetics after ionizing radiation DNA repair High 18773976
2009 SETMAR interacts with TopoIIα in acute leukemia and breast cancer cells; SETMAR enhances TopoIIα decatenation activity in vitro; reducing SETMAR expression increases decatenation checkpoint arrest and sensitizes cells to TopoIIα inhibitors. Co-immunoprecipitation, in vitro kDNA decatenation assay, siRNA knockdown, flow cytometry (checkpoint assay) Blood / PloS one High 19390626 19458360
2010 Crystal structure of the SETMAR transposase catalytic domain reveals a dimeric enzyme with unusual active site plasticity; the F460K dimerization mutant abolishes DNA cleavage, DNA binding, and NHEJ activities, demonstrating that dimerization is required for enzymatic and repair functions. X-ray crystallography (2.37 Å), dimerization mutant analysis, in vitro DNA cleavage and binding assays, NHEJ functional assay Biochemistry High 20521842
2010 SETMAR co-immunoprecipitates with PCNA and RAD9 (member of the RAD9-HUS1-RAD1 checkpoint complex); SETMAR knockdown causes a marked defect in restart of stalled replication forks and sensitizes cells to replication stress; SETMAR also promotes TopoIIα-mediated relaxation of positively supercoiled DNA. Co-immunoprecipitation, hydroxyurea-induced replication stress assay, replication fork restart assay (DNA fiber), γ-H2AX/RAD51 foci analysis, in vitro supercoil relaxation assay Nucleic acids research High 20457750
2010 When hPso4 forms a complex with SETMAR, hPso4 is solely responsible for DNA binding in the complex and negatively regulates SETMAR's TIR binding activity, redirecting SETMAR to non-TIR sites such as DSBs. DNA binding competition assay, stoichiometric analysis, electrophoretic mobility shift assay Archives of biochemistry and biophysics Medium 20416268
2011 SETMAR possesses endonuclease activity that preferentially cleaves ssDNA and ssDNA overhangs of partial duplex DNA; the D483A catalytic mutant lacking endonuclease activity fails to stimulate DNA end joining in cell extracts, establishing this nuclease activity as essential for NHEJ function. In vitro endonuclease assay with purified protein, cell extract-based NHEJ assay with mutant rescue Biochemistry High 21491884
2012 Chk1 phosphorylates SETMAR specifically at Ser495 in vivo in response to ionizing radiation; the S495A mutant is defective in DSB-induced chromatin association and fails to enhance DSB repair, whereas it shows increased replication fork restart compared to wild-type, demonstrating that Chk1-mediated phosphorylation differentially regulates these two SETMAR functions. In vivo phosphorylation mapping, site-directed mutagenesis, chromatin association assay, DSB repair assay, replication fork restart assay Oncogene High 22231448
2012 The DDN catalytic motif (N610) of SETMAR's transposase domain is required for ssDNA binding and cleavage of ssDNA overhangs and pseudo-replication fork substrates; substitution with DDD or DDE (restoring ancestral motif) reduces ssDNA binding and abolishes this cleavage activity, impairing NHEJ repair and replication fork restart in vivo. Site-directed mutagenesis, in vitro ssDNA cleavage and binding assays with fork substrates, in vivo NHEJ and replication restart assays The Journal of biological chemistry High 24573677
2013 SETMAR (Metnase) and Artemis both possess endonuclease activities that trim 3' overhangs of DSB ends; SETMAR cleaves overhangs with sequence dependence and cleaves into the duplex region near the overhang; SETMAR efficiently trims 3'-phosphoglycolate-terminated overhangs; however, in cell-extract-based end-joining systems, Artemis but not SETMAR efficiently stimulates ligation of unligatable 3'-PG overhangs. In vitro endonuclease assay with modified DNA substrates, human cell extract-based end-joining reconstitution DNA repair High 23602515
2014 Phosphorylated SETMAR feeds back to increase Chk1 stability by decreasing Chk1 interaction with DDB1, thereby reducing Chk1 ubiquitination and proteasomal degradation mediated by Cul4A. Co-immunoprecipitation, ubiquitination assay, protein half-life measurement Cell division Medium 25024738
2015 Using quantitative proteomic analysis of methylated lysines, SETMAR was identified to methylate lysine 130 of the mRNA splicing factor snRNP70 in vitro and in cells, primarily generating monomethylation at this position; this is proposed to regulate 5' splice site selection. Quantitative proteomics (SILAC-based), in vitro methyltransferase assay, cellular methylation validation The Journal of biological chemistry High 25795785
2015 The SET domain of SETMAR (but not its H3K36me2 activity per se) is required for cleavage of the 5' end of ssDNA overhangs on fork and non-fork substrates in vitro, and for recovery from hydroxyurea-induced replication fork stalling in vivo. SET domain deletion mutant analysis, in vitro ssDNA overhang cleavage assay, hydroxyurea replication restart assay PloS one Medium 26437079
2016 SETMAR associates with Exonuclease 1 (Exo1) and mediates loading of Exo1 onto ssDNA overhangs at stalled replication forks; SETMAR's DNA binding activity (not its cleavage activity) is required to facilitate Exo1-mediated 5' strand resection on lagging strand daughter DNA. Co-immunoprecipitation, in vitro Exo1 loading and resection assay with stalled fork substrates, domain mutant analysis The Journal of biological chemistry High 27974460
2019 The DNA-binding domain of SETMAR's transposase targets the enzyme to transposon-end remnants (Hsmar1 TIRs) in the human genome, and this targeting enables regulation of gene expression dependent on the methylase activity; overexpression of wild-type SETMAR (but not methylase-deficient SETMAR) changes expression of ~1500 genes >2-fold. ChIP, transcriptomic analysis, methylase-deficient mutant comparison in human cells Nucleic acids research Medium 30329085
2020 NONO regulates alternative splicing of SETMAR pre-mRNA (specifically exon skipping) by binding to its cognate motif via the RRM2 domain; NONO directly interacts with SFPQ to regulate this splicing event; the long SETMAR isoform (SETMAR-L) produced in this manner suppresses metastasis by inducing H3K27me3 at promoters of metastatic oncogenes. RNA immunoprecipitation, splice-switching functional assays, Co-IP (NONO-SFPQ), overexpression rescue experiments Molecular therapy Medium 32950106
2020 SETMAR upregulation in radiation-resistant glioblastoma residual cells mediates high H3K36me2, causing global euchromatization and efficient recruitment of NHEJ proteins (Ku80) to DSBs; conditional SETMAR knockdown or H3K36A mutation prevents Ku80 retention at DSBs and compromises NHEJ repair, leading to senescence or apoptosis. SETMAR knockdown, H3K36A mutant cells, Ku80 ChIP at DSBs, NHEJ assay, orthotopic mouse model Neuro-oncology High 32458986
2022 Crystal structure of SETMAR DNA-binding domain (DBD) in complex with TIR DNA at 2.37 Å resolution shows SETMAR forms a dimeric complex with each DBD bound to TIR DNA through 32 hydrogen bonds; ChIP-seq confirms ~5000 primary TIR binding sites genome-wide; SETMAR KO alters expression of 163 genes and causes 233 alternative splicing events, including splicing factors and neuronal genes. X-ray crystallography (2.37 Å), ChIP-seq, CRISPR/Cas9 KO with RNA-seq and alternative splicing analysis The Journal of biological chemistry High 35378129
2024 SETMAR methylates dimethylated H3K36 at the SMARCA2 promoter to promote SMARCA2 transcription; SMARCA2 then binds enhancers of thyroid differentiation transcription factors PAX8 and FOXE1 to promote chromatin accessibility and their expression; additionally, METTL3-mediated m6A modification of SETMAR mRNA controls SETMAR expression in an IGF2BP3-dependent manner. ChIP, chromatin accessibility assay (ATAC-seq), methyltransferase assay, m6A sequencing, loss-of-function and rescue experiments Advanced science Medium 38900084
2026 O-GlcNAcylation of NONO at Ser147 stabilizes NONO interaction with SFPQ and promotes alternative splicing of SETMAR pre-mRNA, favoring the long isoform; loss of this O-GlcNAcylation leads to production of truncated SETMAR-S, which reduces H3K36me2 and impairs Ku70 recruitment to DSBs, compromising NHEJ repair. O-GlcNAcylation site mutagenesis, co-IP (NONO-SFPQ), splicing assay, H3K36me2 ChIP, Ku70 recruitment at DSBs, irradiation survival assays in vitro and in vivo Genome biology Medium 41535889

Source papers

Stage 0 corpus · 45 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 The SET domain protein Metnase mediates foreign DNA integration and links integration to nonhomologous end-joining repair. Proceedings of the National Academy of Sciences of the United States of America 123 16332963
2007 The ancient mariner sails again: transposition of the human Hsmar1 element by a reconstructed transposase and activities of the SETMAR protein on transposon ends. Molecular and cellular biology 94 17403897
2006 The human SETMAR protein preserves most of the activities of the ancestral Hsmar1 transposase. Molecular and cellular biology 83 17130240
2020 NONO Inhibits Lymphatic Metastasis of Bladder Cancer via Alternative Splicing of SETMAR. Molecular therapy : the journal of the American Society of Gene Therapy 69 32950106
2008 Human Pso4 is a metnase (SETMAR)-binding partner that regulates metnase function in DNA repair. The Journal of biological chemistry 68 18263876
2009 Metnase mediates chromosome decatenation in acute leukemia cells. Blood 52 19458360
2010 Metnase promotes restart and repair of stalled and collapsed replication forks. Nucleic acids research 51 20457750
2008 The SET and transposase domain protein Metnase enhances chromosome decatenation: regulation by automethylation. Nucleic acids research 51 18790802
2010 Metnase/SETMAR: a domesticated primate transposase that enhances DNA repair, replication, and decatenation. Genetica 44 20309721
2009 Metnase mediates resistance to topoisomerase II inhibitors in breast cancer cells. PloS one 44 19390626
2011 Biochemical characterization of metnase's endonuclease activity and its role in NHEJ repair. Biochemistry 43 21491884
2008 The human set and transposase domain protein Metnase interacts with DNA Ligase IV and enhances the efficiency and accuracy of non-homologous end-joining. DNA repair 40 18773976
2007 Biochemical characterization of a SET and transposase fusion protein, Metnase: its DNA binding and DNA cleavage activity. Biochemistry 40 17877369
2012 Chk1 phosphorylation of Metnase enhances DNA repair but inhibits replication fork restart. Oncogene 33 22231448
2020 Inhibition of SETMAR-H3K36me2-NHEJ repair axis in residual disease cells prevents glioblastoma recurrence. Neuro-oncology 31 32458986
2015 A Proteomic Strategy Identifies Lysine Methylation of Splicing Factor snRNP70 by the SETMAR Enzyme. The Journal of biological chemistry 30 25795785
2012 Targeting the transposase domain of the DNA repair component Metnase to enhance chemotherapy. Cancer research 30 23090115
2014 The DDN catalytic motif is required for Metnase functions in non-homologous end joining (NHEJ) repair and replication restart. The Journal of biological chemistry 28 24573677
2010 The transposase domain protein Metnase/SETMAR suppresses chromosomal translocations. Cancer genetics and cytogenetics 26 20620605
2019 Human SETMAR is a DNA sequence-specific histone-methylase with a broad effect on the transcriptome. Nucleic acids research 24 30329085
2010 Crystal structure of the human Hsmar1-derived transposase domain in the DNA repair enzyme Metnase. Biochemistry 23 20521842
2013 Trimming of damaged 3' overhangs of DNA double-strand breaks by the Metnase and Artemis endonucleases. DNA repair 20 23602515
2013 Study of the interaction among Notch pathway receptors, correlation with stemness, as well as their interaction with CD44, dipeptidyl peptidase-IV, hepatocyte growth factor receptor and the SETMAR transferase, in colon cancer stem cells. Journal of receptor and signal transduction research 20 23964856
2024 SETMAR Facilitates the Differentiation of Thyroid Cancer by Regulating SMARCA2-Mediated Chromatin Remodeling. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 18 38900084
2021 Structure, Activity, and Function of SETMAR Protein Lysine Methyltransferase. Life (Basel, Switzerland) 15 34947873
2017 SETMAR isoforms in glioblastoma: A matter of protein stability. Oncotarget 15 28038463
2016 Metnase Mediates Loading of Exonuclease 1 onto Single Strand Overhang DNA for End Resection at Stalled Replication Forks. The Journal of biological chemistry 15 27974460
2022 Metnase and EEPD1: DNA Repair Functions and Potential Targets in Cancer Therapy. Frontiers in oncology 14 35155245
2015 The SET Domain Is Essential for Metnase Functions in Replication Restart and the 5' End of SS-Overhang Cleavage. PloS one 14 26437079
2010 Regulation of Metnase's TIR binding activity by its binding partner, Pso4. Archives of biochemistry and biophysics 14 20416268
2019 The roles of the human SETMAR (Metnase) protein in illegitimate DNA recombination and non-homologous end joining repair. DNA repair 13 31238295
2011 Neoamphimedine circumvents metnase-enhanced DNA topoisomerase IIα activity through ATP-competitive inhibition. Marine drugs 13 22163192
2020 Distinct roles of structure-specific endonucleases EEPD1 and Metnase in replication stress responses. NAR cancer 11 32743552
2014 The DNA repair component Metnase regulates Chk1 stability. Cell division 11 25024738
2014 Potential role for the Metnase transposase fusion gene in colon cancer through the regulation of key genes. PloS one 11 25333365
2021 Mutation and expression alterations of histone methylation-related NSD2, KDM2B and SETMAR genes in colon cancers. Pathology, research and practice 10 33621919
2022 SETMAR, a case of primate co-opted genes: towards new perspectives. Mobile DNA 8 35395947
2021 Two repeated motifs enriched within some enhancers and origins of replication are bound by SETMAR isoforms in human colon cells. Genomics 8 33812898
2022 Structural and genome-wide analyses suggest that transposon-derived protein SETMAR alters transcription and splicing. The Journal of biological chemistry 7 35378129
2014 Fidelity of end joining in mammalian episomes and the impact of Metnase on joint processing. BMC molecular biology 7 24655462
2021 Genome-wide mapping of binding sites of the transposase-derived SETMAR protein in the human genome. Computational and structural biotechnology journal 6 34377368
2016 Crystallization of and selenomethionine phasing strategy for a SETMAR-DNA complex. Acta crystallographica. Section F, Structural biology communications 3 27599863
2026 O-GlcNAcylation of NONO mediates alternative splicing of SETMAR and facilitates NHEJ repair. Genome biology 0 41535889
2025 A 300 bp non-coding repeat sequence has co-evolved with the ced-2/CRKII-set-23/SETMAR genes of nematodes. microPublication biology 0 41200240
2023 Investigating the Expression Pattern of the SETMAR Gene Transcript Variants in Childhood Acute Leukemia: Revisiting an Old Gene. Journal of pediatric hematology/oncology 0 36706314