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Showing NSMCE2 — MMS21 is a alias.

NSMCE2

E3 SUMO-protein ligase NSE2 · UniProt Q96MF7

Length
247 aa
Mass
27.9 kDa
Annotated
2026-06-10
39 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NSMCE2 (MMS21) is the SUMO E3 ligase subunit of the SMC5/6 complex that safeguards genome stability by sumoylating substrates at sites of replication stress and DNA damage (PMID:16055714, PMID:22751501). It docks through an N-terminal helix bundle onto the coiled-coil arm of SMC5 in a 1:1 complex, while its C-terminal RING-type domain, coordinated by a conserved zinc-binding cysteine, catalyzes SUMO transfer and dictates E2-E3 specificity (PMID:19748359, PMID:21999667, PMID:21324902). This ligase activity is allosterically controlled: ATP binding to SMC5 and conformational remodeling of the SMC5/6 ATPase couple to NSMCE2 catalysis, DNA binding to a positively charged patch in the SMC5 ARM domain acts as a sensor that stimulates the enzyme, and Mec1/ATR-dependent phosphorylation during S-phase further activates it (PMID:25764370, PMID:29769404, PMID:25659338). Through sumoylation of substrates including SMC6, the cohesin subunit SCC1, and TRAX, NSMCE2 counteracts Rad51-dependent recombination intermediates at damaged and stalled forks, cooperates with the BLM/Sgs1 helicase to rescue collapsed forks, and promotes sister chromatid recombination by antagonizing Wapl (PMID:16055714, PMID:17081974, PMID:22751501, PMID:30735491). It additionally drives SUMO-dependent relocation of double-strand breaks to nuclear pores and the nuclear envelope, suppresses gross chromosomal rearrangements, and is required for chromosome cohesion and segregation (PMID:27056668, PMID:29505562, PMID:19502785). SUMO-ligase-independent activities of NSMCE2 are separately required to limit recombination and prevent cancer and premature aging, as a ligase-dead mutant fails to phenocopy full deletion in mice (PMID:26443207). Compound heterozygous frameshift mutations in NSMCE2 cause human primordial dwarfism with insulin resistance and gonadal failure, with the disease phenotype dependent on intact SUMO ligase activity (PMID:25105364).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2005 High

    Established that human MMS21/NSMCE2 is a SUMO E3 ligase whose catalytic activity is required for DNA repair and survival, defining its core enzymatic function.

    Evidence RNAi knockdown with WT vs. ligase-dead rescue, sumoylation and comet assays in HeLa cells

    PMID:16055714

    Open questions at the time
    • Substrate set limited to SMC6 and TRAX
    • Mechanism of substrate selection not addressed
  2. 2006 High

    Placed Mms21 in a distinct sumoylation pathway acting with Sgs1/BLM to counteract recombination intermediates at damaged forks, separating it from other SUMO ligases.

    Evidence 2D gel detection of X-molecules and genetic epistasis in S. cerevisiae

    PMID:17081974

    Open questions at the time
    • Direct sumoylation substrate driving X-structure resolution not identified
    • Biochemical link between Mms21 and Sgs1 unresolved
  3. 2009 High

    Defined the two-domain architecture of NSMCE2 — an SMC5-binding helix bundle and a novel RING SUMO-ligase domain — and quantified the high-affinity 1:1 SMC5 interaction, anchoring its molecular structure.

    Evidence X-ray crystallography, mutagenesis, ITC and limited proteolysis in yeast

    PMID:19748359 PMID:21999667

    Open questions at the time
    • Structure of full SMC5/6-bound complex not resolved
    • How catalysis is regulated in context not shown
  4. 2009 Medium

    Identified an SMC5-MMS21 sub-complex required for mitotic chromosome cohesion independent of SMC6, broadening NSMCE2 function beyond repair into segregation.

    Evidence RNAi, live imaging, gel filtration in human cells

    PMID:19502785

    Open questions at the time
    • Molecular basis of cohesion role unclear
    • Whether sumoylation is required not tested here
  5. 2011 Medium

    Showed Mms21 ligase activity is needed during unperturbed cycles and mapped the catalytic zinc-coordinating cysteine, tying enzyme integrity to chromosome stability.

    Evidence Active-site mutagenesis, checkpoint genetics, chromosome loss assays in yeast

    PMID:21324902

    Open questions at the time
    • Endogenous substrates during normal cycling not defined
    • Single-organism analysis
  6. 2012 High

    Identified SCC1/cohesin as a substrate and placed Mms21-mediated SCC1 sumoylation upstream of Wapl antagonism to promote sister chromatid recombination, providing a concrete substrate-to-phenotype mechanism.

    Evidence Co-IP, non-sumoylatable Scc1 mutant, Wapl epistasis, IR sensitivity assays

    PMID:22751501

    Open questions at the time
    • How SUMO-SCC1 antagonizes Wapl mechanistically unresolved
    • Specific lysines and their individual contributions not dissected
  7. 2012 Medium

    Distinguished NSMCE2 catalytic function from complex assembly, showing ligase activity supports HR and bulky-lesion repair while SMC5/SMC6 association is ligase-independent.

    Evidence DT40 knockout with ligase-dead rescue, gel filtration, comet and HR assays

    PMID:22921571

    Open questions at the time
    • Substrates for bulky-lesion repair not identified
    • Why Smc5 but not Smc6 is destabilized unexplained
  8. 2013 Medium

    Resolved that the SUMO-ligase domain destabilizes early D-loops and resolves joint molecules in meiosis, separating Mms21 catalytic from Smc6 structural contributions to recombination control.

    Evidence Southern blotting for joint molecules and genetic epistasis in yeast meiosis

    PMID:24385936

    Open questions at the time
    • Direct substrate at joint molecules not identified
    • Meiosis-specific regulation unclear
  9. 2014 High

    Linked NSMCE2 to a human Mendelian disease, demonstrating SUMO-ligase-dependent prevention of primordial dwarfism, insulin resistance and gonadal failure.

    Evidence Patient cells, WT vs. ligase-dead rescue, zebrafish knockdown, micronucleus and BLM foci assays

    PMID:25105364

    Open questions at the time
    • Tissue-specific basis of growth/metabolic phenotype unexplained
    • Substrates underlying disease not defined
  10. 2015 High

    Revealed allosteric coupling of SMC5 ATP binding and ATPase-driven conformational remodeling to NSMCE2 catalysis, showing the enzyme is integrated with SMC5/6 mechanochemistry.

    Evidence In vitro sumoylation with ATPase mutants, scanning force microscopy in yeast

    PMID:25764370

    Open questions at the time
    • Structural intermediates of remodeling not captured
    • How ATPase cycle times sumoylation in vivo unclear
  11. 2015 High

    Separated SUMO-ligase-dependent from -independent NSMCE2 functions in vivo, showing the latter are critical for cancer suppression and aging prevention and are synthetic lethal with BLM loss.

    Evidence Conditional mouse knockout, ligase-dead knock-in, B-cell double KO, SCE and micronuclei assays

    PMID:26443207

    Open questions at the time
    • Molecular identity of the ligase-independent activity unknown
    • How NSMCE2 and BLM converge mechanistically unresolved
  12. 2015 Medium

    Established Mec1/ATR-dependent phosphorylation as a positive S-phase regulator of Mms21 ligase activity, connecting the DNA damage checkpoint to SUMO output.

    Evidence MS phosphosite mapping (S260/S261), non-phosphorylatable mutants, ligase and chromosome loss assays in yeast

    PMID:25659338

    Open questions at the time
    • Conservation of the phosphosites in human NSMCE2 not tested
    • Structural effect of phosphorylation unknown
  13. 2016 High

    Defined DNA binding to the SMC5 ARM domain as a sensor that allosterically activates NSMCE2, showing the enzyme is switched on at DNA.

    Evidence In vitro DNA-stimulated sumoylation assay, ARM-domain mutagenesis, damage sensitivity assays

    PMID:29769404

    Open questions at the time
    • Whether specific DNA structures preferentially activate it not resolved
    • Integration with ATPase and phospho-activation not unified
  14. 2016 Medium

    Mapped SUMO-form-specific DSB relocation: polySUMOylation recruits the STUbL Slx5/Slx8 to move breaks to nuclear pores, while monoSUMOylation drives breaks to the SUN protein Mps3.

    Evidence High-resolution live imaging and cell-cycle-specific genetic epistasis in yeast

    PMID:27056668

    Open questions at the time
    • SUMOylated targets driving each relocation route not identified
    • Mammalian conservation untested
  15. 2016 Medium

    Connected NSMCE2/SMC5/6 to topoisomerase II via physical interaction with TOP2A and selective etoposide sensitivity, implicating it in resolving TOP2A-mediated repair intermediates.

    Evidence CRISPR knockout, etoposide/IR sensitivity, Co-IP/MS in U2OS cells

    PMID:27792189

    Open questions at the time
    • Whether TOP2A is a sumoylation substrate not established
    • Direct vs. indirect interaction not resolved
  16. 2018 Medium

    Showed Mms21 ligase activity suppresses duplication-mediated gross chromosomal rearrangements through a pathway distinct from Sgs1, refining its anti-rearrangement role.

    Evidence GCR assays, WGS, Rad52/Ddc2 foci, epistasis in yeast

    PMID:29505562

    Open questions at the time
    • Substrate suppressing NAHR-driven GCRs unknown
    • Human relevance not tested
  17. 2019 Medium

    Demonstrated NSMCE2 is required for collapsed-fork rescue in human cells, governing RAD51 turnover and BLM recruitment, and acting epistatically with BLM at stalled forks.

    Evidence siRNA, hydroxyurea, DNA fiber analysis, RAD51/BLM foci, SCE assays

    PMID:30735491

    Open questions at the time
    • Substrate controlling RAD51 persistence not identified
    • Mechanism of BLM recruitment unresolved
  18. 2021 Medium

    Identified Esc2 as a factor that recruits Ubc9 to confer Mms21 substrate specificity, defining a mechanism shaping the Mms21 sumoylation proteome (nucleolar, SMC, and MCM targets).

    Evidence Proteome-wide SUMO profiling, GCR assays, Esc2 mutagenesis in yeast

    PMID:33600463

    Open questions at the time
    • Whether a human Esc2 equivalent regulates NSMCE2 unknown
    • Functional roles of individual sumoylated targets undefined
  19. 2025 Low

    Proposed a pro-tumorigenic role in hepatocellular carcinoma via SUMOylation of PPARα that blocks its degradation and activates the PPARα-CYP7A1 axis, extending NSMCE2 substrates beyond genome maintenance.

    Evidence Co-IP, SUMOylation and ubiquitination assays, HCC models

    PMID:40318278

    Open questions at the time
    • Single Co-IP without reciprocal validation of the PPARα interaction
    • SUMO acceptor sites on PPARα not mapped
    • Independent confirmation lacking
  20. 2026 Low

    Indicated the extreme C-terminus of Mms21 fine-tunes both ligase-dependent and -independent functions by opposing an adjacent domain, refining the structure-function map.

    Evidence C-terminal truncation mutants, growth, damage sensitivity and cell-cycle assays in yeast

    PMID:41949878

    Open questions at the time
    • No direct biochemical mechanism for the C-terminal effect
    • Single organism, phenotypic only
    • Conservation in human NSMCE2 untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular identity of NSMCE2's SUMO-ligase-independent activities, and the full substrate set linking sumoylation to specific fork-rescue, recombination, and disease phenotypes, remain undefined.
  • Ligase-independent function biochemically unidentified
  • Human substrates beyond SCC1/SMC6 largely uncatalogued
  • Unified model integrating ATPase, DNA-sensing, and phospho-activation lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 5 GO:0140096 catalytic activity, acting on a protein 3 GO:0098772 molecular function regulator activity 2 GO:0003677 DNA binding 1
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2
Pathway
R-HSA-73894 DNA Repair 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-1640170 Cell Cycle 2 R-HSA-69306 DNA Replication 2
Partners
PPARASCC1SMC5SMC6TOP2ATRAX
Complex memberships
SMC5/6 complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Human MMS21/NSMCE2 functions as a SUMO E3 ligase that stimulates sumoylation of hSMC6 and the DNA repair protein TRAX. Depletion by RNAi sensitizes HeLa cells to DNA damage-induced apoptosis, and this hypersensitivity is rescued by wild-type hMMS21 but not its ligase-inactive mutant, establishing that SUMO ligase activity is required for DNA repair and prevention of apoptosis. RNAi knockdown, ectopic expression of WT vs. ligase-inactive mutant, sumoylation assay, comet assay, phospho-CHK2 foci imaging Molecular and cellular biology High 16055714
2006 In S. cerevisiae, Mms21 SUMO ligase activity (together with Ubc9) counteracts Rad51-dependent accumulation of cruciform/X-structures at damaged replication forks, acting in concert with Sgs1/BLM to resolve these intermediates. mms21 mutants phenocopy ubc9 mutants but not siz1, srs2, or pcna sumoylation mutants, placing Mms21 in a distinct sumoylation pathway. 2D gel electrophoresis to detect X-molecules, genetic epistasis analysis, mutant characterization Cell High 17081974
2009 Crystal structure of yeast Mms21 in complex with the Smc5 arm domain revealed two functional domains: an N-terminal half forming a helix bundle with the Smc5 coiled-coil for Smc5 binding, and a C-terminal SUMO ligase domain adopting a novel RING E3 structure. Mutagenesis showed the Mms21-Smc5 interface is required for cell growth and DNA damage resistance, while the RING domain confers specificity to SUMO E2-E3 interaction. X-ray crystallography, mutagenesis, functional complementation assays Molecular cell High 19748359
2009 Mms21 interacts with Smc5 at the coiled-coil arm region in a 1:1 stoichiometry with Kd of 0.68 µM, as determined by limited proteolysis, mass spectrometry, N-terminal sequencing, and isothermal titration calorimetry. Limited proteolysis, mass spectrometry, N-terminal sequencing, isothermal titration calorimetry Biochemistry High 21999667
2009 SMC5 and MMS21 (but not SMC6) are required for chromosome cohesion and mitotic progression; ablation of either SMC5 or MMS21 leads to premature sister chromatid separation prior to anaphase and spindle assembly checkpoint activation. Mitotic SMC5 co-elutes with MMS21 but not SMC6, suggesting a cohesion-specific SMC5-MMS21 sub-complex. RNAi knockdown, live cell imaging/microscopy, gel filtration chromatography Cell cycle (Georgetown, Tex.) Medium 19502785
2011 Mms21 SUMO ligase activity is required during unperturbed mitotic cell cycle in S. cerevisiae; ligase-defective cells accumulate spontaneous DNA damage, require Mec1 checkpoint for survival, and show increased chromosome breakage and loss. A conserved cysteine (C221) coordinating the zinc ion in Loop 2 of the SPL-RING domain is essential for catalytic activity. SUMO ligase mutant analysis, checkpoint genetics, chromosome loss assays, site-directed mutagenesis The Journal of biological chemistry Medium 21324902
2012 Mms21 sumoylates multiple lysines of the cohesin subunit Scc1; Scc1 sumoylation promotes sister chromatid recombination (SCR) at DSBs in S/G2 cells. Cells expressing non-sumoylatable Scc1 (15KR) are defective in SCR and sensitive to ionizing radiation. Depletion of Wapl (a negative cohesin regulator) rescues SCR defects of Mms21-deficient or Scc1 15KR cells, placing Mms21-mediated Scc1 sumoylation upstream of Wapl antagonism. Co-IP, laser-induced damage foci, sumoylation assays, genetic epistasis with Wapl depletion, IR sensitivity assays Genes & development High 22751501
2012 In chicken DT40 cells, Nse2 SUMO ligase activity is required for efficient repair of bulky DNA lesions and homologous recombination, but not for Smc5/6 complex assembly. Nse2 deficiency destabilizes Smc5 but not Smc6. Smc5/Smc6 association is independent of Nse2. Gene knockout (DT40), complementation with SUMO ligase mutant, gel filtration, comet assay, HR assays DNA repair Medium 22921571
2013 In budding yeast meiosis, Smc5/6-Mms21 antagonizes rogue joint molecule (JM) intermediates via two mechanisms: destabilizing early recombination intermediates (D-loops) and resolving JMs. Loss of Mms21 SUMO E3-ligase domain causes transient JM accumulation dependent on Mus81-Mms4 for resolution; loss of Smc6 causes persistent JM accumulation and failure of chromatin separation. Genetic analysis, Southern blotting for JM detection, epistasis with Mus81-Mms4 and BLM/Sgs1 PLoS genetics Medium 24385936
2014 Compound heterozygous frameshift mutations in NSMCE2 in humans cause primordial dwarfism, extreme insulin resistance, and gonadal failure. Patient cells show increased micronuclei/nucleoplasmic bridges, delayed DNA synthesis recovery, and reduced BLM foci after replication fork stalling. Nuclear abnormalities are rescued by WT NSMCE2 but not by a SUMO-ligase-inactive mutant. Zebrafish nsmce2 knockdown produces dwarfism rescued by WT but not ligase-dead NSMCE2. Patient cell analysis, WT vs. ligase-dead mutant rescue, zebrafish knockdown, micronucleus assay, BLM foci imaging The Journal of clinical investigation High 25105364
2015 Mms21 SUMO ligase activity depends on ATP binding to Smc5; the ATPase activity of the Smc5/6 complex is mechanistically coupled to Mms21 E3 function through the coiled-coil domain of Smc5, enabling conformational remodeling of the Smc5-Mms21 heterodimer as visualized by scanning force microscopy. Mms21 sumoylation assays, ATPase mutants, scanning force microscopy, chromosome disjunction assays PLoS biology High 25764370
2015 In mice, complete NSMCE2 deletion in adult animals causes pathologies resembling Bloom's syndrome (increased recombination, micronuclei accumulation, cancer, premature aging). A SUMO-ligase-compromising mutation has no detectable impact on murine lifespan, indicating SUMO-ligase-independent activities of NSMCE2 are critical for cancer suppression and aging prevention. Concomitant deletion of Blm and Nsmce2 is synthetic lethal in B lymphocytes. Conditional mouse knockout, SUMO ligase point mutant knock-in, B-cell-specific double KO, SCE assay, micronuclei counting The EMBO journal High 26443207
2015 Mms21 is phosphorylated by the DNA damage kinase Mec1 at S260 and S261 (C-terminal Mec1/Tel1 consensus motif) during S-phase. Non-phosphorylatable substitutions reduce SUMO ligase activity, increase MMS sensitivity, and increase chromosome loss, establishing Mec1-dependent phosphorylation as a positive regulator of Mms21 SUMO ligase activity. Mass spectrometry phosphosite mapping, non-phosphorylatable mutant analysis, SUMO ligase activity assays, chromosome loss assays DNA repair Medium 25659338
2016 In S/G2-phase cells, Mms21-mediated polySUMOylation (together with Siz2) on DNA damage recruits the STUbL Slx5/Slx8, which mediates DSB relocation to nuclear pores. In S-phase, monoSUMOylation by the Rtt107-stabilized SMC5/6-Mms21 complex drives DSBs to the SUN domain protein Mps3 independently of Slx5. High-resolution live imaging, genetic epistasis (slx5, slx8, mps3 mutants), cell-cycle-specific analysis Genes & development Medium 27056668
2016 NSMCE2-deficient human U2OS cells show increased sensitivity to the topoisomerase II inhibitor etoposide but not to ionizing radiation. Immunoprecipitation/mass spectrometry reveals that the SMC5/6 complex physically interacts with DNA topoisomerase IIα (TOP2A), suggesting a role in resolving TOP2A-mediated DSB-repair intermediates during replication. CRISPR-Cas9 knockout, etoposide/IR sensitivity assays, co-immunoprecipitation, mass spectrometry International journal of molecular sciences Medium 27792189
2016 Mms21 SUMO ligase activity interacts epistatically with topoisomerase-1 (Top1) in maintaining longer chromosomes; mms21sl top1 double mutants preferentially destabilize longer chromosomes/YACs and display synthetic sickness, while smc6-56 top1 double mutants do not show this preferential destabilization, indicating specificity to Mms21 sumoylation. Genetic epistasis, YAC stability assays, synthetic sickness analysis Current genetics Low 27872982
2018 The Nse2/Mms21 SUMO E3 ligase in the Smc5/6 complex is directly stimulated by DNA binding. Activation requires electrostatic interaction between DNA and a positively charged patch in the ARM domain of Smc5, which acts as a DNA sensor that allosterically activates Nse2 E3 activity. Disruption of the ARM-DNA interaction sensitizes cells to DNA damage. In vitro SUMO ligase assay with DNA, mutagenesis of ARM domain, DNA damage sensitivity assays The EMBO journal High 29769404
2018 Mms21 SUMO ligase activity suppresses duplication-mediated gross chromosomal rearrangements (dGCRs) formed by non-allelic homologous recombination through Rad52-, Rrm3-, and Pol32-dependent break-induced replication. Combining mms21-CH (ligase-inactive) with sgs1Δ causes synergistic GCR increase, establishing distinct roles for Mms21 and Sgs1 in GCR suppression. GCR assays, whole-genome sequencing, Rad52/Ddc2 foci quantification, genetic epistasis PLoS genetics Medium 29505562
2019 NSMCE2 is required for rescue of collapsed replication forks in human cells; NSMCE2-deficient cells fail to accumulate DSBs during converging fork rescue, accumulate excess persistent RAD51, and fail to recruit BLM to stalled forks, leading to un-rescued forks persisting into mitosis and increased mitotic DNA damage. In cells deficient in both NSMCE2 and BLM, HU-induced DSBs and SCE levels resemble NSMCE2-deficient levels. siRNA knockdown, hydroxyurea treatment, DNA fiber analysis, RAD51/BLM foci imaging, SCE assay, mitotic DNA damage quantification PLoS genetics Medium 30735491
2021 Esc2 (a protein with SUMO-like domains) recruits the Ubc9 SUMO-conjugating enzyme to specifically facilitate Mms21-dependent sumoylation and suppress dGCRs. The Esc2 D430R mutation impairs Ubc9 binding and specifically down-regulates sumoylation of Mms21-preferred targets (nucleolar proteins, SMC complex components, MCM helicase), as shown by proteome-wide SUMO analysis. GCR assays, proteome-wide SUMOylation profiling (mass spectrometry), genetic epistasis, mutagenesis PloS one Medium 33600463
2025 NSMCE2 promotes hepatocellular carcinoma by SUMOylating PPARα, thereby reducing PPARα ubiquitination-mediated degradation and activating the PPARα-CYP7A1 axis. NSMCE2-PPARα interaction was confirmed by co-immunoprecipitation. Co-immunoprecipitation, in vivo and in vitro HCC models, SUMOylation assay, ubiquitination assay International immunopharmacology Low 40318278
2026 The C-terminus of Mms21 (last 22 amino acids, beyond the RING/E3 domain) contributes to both ligase-dependent and ligase-independent functions; truncation (mms21Δ22) causes slower growth, increased DNA damage sensitivity, G2-M delay, and reduced Mms21 protein levels beyond what is attributable to protein reduction alone. The C-terminus appears to fine-tune ligase activity by opposing an adjacent domain. Site-directed truncation mutants, growth assays, DNA damage sensitivity, cell cycle analysis, protein quantification Molecular biology of the cell Low 41949878

Source papers

Stage 0 corpus · 39 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Ubc9- and mms21-mediated sumoylation counteracts recombinogenic events at damaged replication forks. Cell 247 17081974
2005 Human MMS21/NSE2 is a SUMO ligase required for DNA repair. Molecular and cellular biology 205 16055714
2016 PolySUMOylation by Siz2 and Mms21 triggers relocation of DNA breaks to nuclear pores through the Slx5/Slx8 STUbL. Genes & development 106 27056668
2014 Hypomorphism in human NSMCE2 linked to primordial dwarfism and insulin resistance. The Journal of clinical investigation 84 25105364
2009 Structural and functional insights into the roles of the Mms21 subunit of the Smc5/6 complex. Molecular cell 77 19748359
2012 Scc1 sumoylation by Mms21 promotes sister chromatid recombination through counteracting Wapl. Genes & development 74 22751501
2013 Smc5/6-Mms21 prevents and eliminates inappropriate recombination intermediates in meiosis. PLoS genetics 63 24385936
2015 NSMCE2 suppresses cancer and aging in mice independently of its SUMO ligase activity. The EMBO journal 55 26443207
2009 The Yin and Yang of the MMS21-SMC5/6 SUMO ligase complex in homologous recombination. DNA repair 48 19217832
2018 DNA activates the Nse2/Mms21 SUMO E3 ligase in the Smc5/6 complex. The EMBO journal 45 29769404
2014 8q24 amplified segments involve novel fusion genes between NSMCE2 and long noncoding RNAs in acute myelogenous leukemia. Journal of hematology & oncology 42 25245984
2011 The Nse2/Mms21 SUMO ligase of the Smc5/6 complex in the maintenance of genome stability. FEBS letters 41 21550342
2015 ATPase-dependent control of the Mms21 SUMO ligase during DNA repair. PLoS biology 37 25764370
2019 Rescue of collapsed replication forks is dependent on NSMCE2 to prevent mitotic DNA damage. PLoS genetics 33 30735491
2009 SMC5 and MMS21 are required for chromosome cohesion and mitotic progression. Cell cycle (Georgetown, Tex.) 33 19502785
2016 Non-SMC Element 2 (NSMCE2) of the SMC5/6 Complex Helps to Resolve Topological Stress. International journal of molecular sciences 25 27792189
2011 Small ubiquitin-related modifier ligase activity of Mms21 is required for maintenance of chromosome integrity during the unperturbed mitotic cell division cycle in Saccharomyces cerevisiae. The Journal of biological chemistry 24 21324902
2018 Mms21: A Putative SUMO E3 Ligase in Candida albicans That Negatively Regulates Invasiveness and Filamentation, and Is Required for the Genotoxic and Cellular Stress Response. Genetics 19 30530734
2018 SUMO E3 ligase Mms21 prevents spontaneous DNA damage induced genome rearrangements. PLoS genetics 16 29505562
2017 Trivial role for NSMCE2 during in vitro proliferation and differentiation of male germline stem cells. Reproduction (Cambridge, England) 16 28576919
2021 The SUMO ligase MMS21 profoundly influences maize development through its impact on genome activity and stability. PLoS genetics 13 34695110
2012 SUMO ligase activity of vertebrate Mms21/Nse2 is required for efficient DNA repair but not for Smc5/6 complex stability. DNA repair 13 22921571
2016 Interplay between Top1 and Mms21/Nse2 mediated sumoylation in stable maintenance of long chromosomes. Current genetics 10 27872982
2015 Mec1-dependent phosphorylation of Mms21 modulates its SUMO ligase activity. DNA repair 10 25659338
2016 Mms21 SUMO Ligase Activity Promotes Nucleolar Function in Saccharomyces cerevisiae. Genetics 9 27510371
2020 A natural variant of the essential host gene MMS21 restricts the parasitic 2-micron plasmid in Saccharomyces cerevisiae. eLife 8 33063663
2022 Identification of BRIP1, NSMCE2, ANAPC7, RAD18 and TTL from chromosome segregation gene set associated with hepatocellular carcinoma. Cancer genetics 6 36126360
2021 Shared and distinct roles of Esc2 and Mms21 in suppressing genome rearrangements and regulating intracellular sumoylation. PloS one 6 33600463
1981 Hyper-recombination and mutator effects of the mms9-1, mms13-1, and mms21-1 mutations in Saccharomyces cerevisiae. Current genetics 6 24185997
2011 Interaction mapping between Saccharomyces cerevisiae Smc5 and SUMO E3 ligase Mms21. Biochemistry 5 21999667
2015 Effects of Nephrolithiasis on Serum DNase (Deoxyribonuclease I and II) Activity and E3 SUMO-Protein Ligase NSE2 (NSMCE2) in Malaysian Individuals. Biomedical and environmental sciences : BES 4 26464253
2009 Purification, crystallization and preliminary X-ray crystallographic studies of the complex between Smc5 and the SUMO E3 ligase Mms21. Acta crystallographica. Section F, Structural biology and crystallization communications 4 19652357
2008 Allelism of Saccharomyces cerevisiae gene PSO10, involved in error-prone repair of psoralen-induced DNA damage, with SUMO ligase-encoding MMS21. Current genetics 4 18437386
2023 The SMC5/6 complex subunit MMS21 regulates stem cell proliferation in rice. Plant cell reports 3 37178216
2024 A Novel NUTM1-NSMCE2 Fusion Gene in a Pediatric Chest NUT Carcinoma. Journal of pediatric hematology/oncology 2 38775398
2025 NSMCE2 promotes the occurrence and development of HCC by regulating the SUMOylation of PPARα. International immunopharmacology 1 40318278
2025 VIRMA Accelerates the Tumorigenesis of Prostate Cancer via Regulating the m6A Modification of NSMCE2 to Eliminate the Generation of Reactive Oxygen Species. International journal of urology : official journal of the Japanese Urological Association 1 40459180
2026 NSMCE2 dispensability in mouse spermatogenesis suggests functional redundancy within the meiotic repair network. Frontiers in cell and developmental biology 0 41853249
2026 Ligase-dependent and independent functions of the C-terminus of Mms21 contribute to optimal growth and genome stability in Saccharomyces cerevisiae. Molecular biology of the cell 0 41949878

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