Affinage

NSMCE2

E3 SUMO-protein ligase NSE2 · UniProt Q96MF7

Length
247 aa
Mass
27.9 kDa
Annotated
2026-04-29
49 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NSMCE2 (MMS21) is the SUMO E3 ligase subunit of the SMC5/6 complex, essential for resolution of recombination intermediates at damaged and stalled replication forks, sister chromatid cohesion during DNA repair, and faithful chromosome segregation. Its N-terminal helix bundle docks onto the Smc5 coiled-coil arm while its C-terminal SP-RING domain catalyzes SUMO transfer via SIM-mediated engagement of the Ubc9–SUMO thioester; ligase activity is allosterically stimulated by ATP binding to Smc5 and by direct DNA contact with the Smc5 ARM domain, and is further upregulated by Mec1-dependent phosphorylation (PMID:19748359, PMID:34853311, PMID:25764370, PMID:29769404, PMID:25659338). Key substrates include SMC6, cohesin subunit Scc1 (whose sumoylation promotes sister chromatid recombination and counteracts Wapl), and PPARα; loss of NSMCE2 leads to unresolved replication intermediates, excess RAD51 accumulation, micronuclei, and mitotic DNA damage (PMID:16055714, PMID:22751501, PMID:30735491, PMID:17081974). Compound heterozygous loss-of-function mutations in NSMCE2 cause primordial dwarfism with extreme insulin resistance and genomic instability in humans (PMID:25105364).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2003 High

    Identifying Nse2 as a core subunit of the Smc5-6 complex essential for viability and homologous recombination-based DSB repair established that this previously uncharacterized protein operates within a defined chromosome maintenance machine.

    Evidence Co-IP/mass spectrometry of the Smc5-6 complex and genetic epistasis with Rhp51/Rad51 in fission yeast

    PMID:12966087

    Open questions at the time
    • Enzymatic activity of Nse2 was unknown
    • Direct physical interaction surface was uncharacterized
    • Whether Nse2 function extended beyond DSB repair was untested
  2. 2005 High

    Demonstrating that Nse2/NSMCE2 is a SUMO E3 ligase — sumoylating SMC6 and other substrates via its SP-RING domain — resolved the molecular activity of the subunit and showed that ligase-dead mutations phenocopy loss-of-function for DNA damage repair but not for essential viability in yeast.

    Evidence In vitro sumoylation assays with SP-RING mutagenesis in fission yeast and human cells; RNAi rescue experiments in HeLa cells

    PMID:15601841 PMID:16055714

    Open questions at the time
    • Structural basis of Smc5–Nse2 docking was unknown
    • How ligase activity is regulated remained open
    • Full substrate repertoire was uncharacterized
  3. 2006 High

    Placing Mms21 in a genetic pathway with Ubc9 and Sgs1/BLM for resolution of cruciform structures at damaged replication forks established its specific replication-associated function, distinct from the Siz1/PCNA sumoylation pathway.

    Evidence 2D gel electrophoresis of replication intermediates and genetic epistasis in budding yeast

    PMID:17081974

    Open questions at the time
    • Whether Mms21 directly sumoylated replication fork substrates was unknown
    • Relationship to mammalian BLM was untested
  4. 2009 High

    The crystal structure of the Mms21–Smc5 complex revealed the bipartite architecture — N-terminal helix bundle for Smc5 binding, C-terminal SP-RING for E3 activity — and showed that the Smc5 interface is essential for both growth and DNA damage resistance.

    Evidence X-ray crystallography with site-directed mutagenesis and yeast functional assays

    PMID:19748359

    Open questions at the time
    • How the E3 engages the E2–SUMO thioester was structurally unresolved
    • Allosteric regulation by ATPase or DNA was unknown
  5. 2009 Medium

    Knockdown of NSMCE2 in human cells revealed a mitotic role — premature sister chromatid separation, checkpoint activation, and mitotic arrest — extending its function beyond S-phase DNA repair.

    Evidence siRNA knockdown in human cells, chromosome spreading, gel filtration chromatography

    PMID:19502785

    Open questions at the time
    • Whether mitotic function requires SUMO ligase activity specifically was not tested
    • The gel filtration-suggested SMC5–MMS21 subcomplex lacks independent validation
  6. 2011 Medium

    Showing that Nse2 SUMO ligase activity suppresses spontaneous Top1 cleavage complexes and that loss of this activity causes hyper-recombination via a NER-parallel pathway broadened the range of endogenous lesions managed by the SMC5/6–Nse2 axis.

    Evidence ChIP-qPCR for Top1cc levels and genetic epistasis in fission yeast

    PMID:21408210

    Open questions at the time
    • Whether Top1 itself is a direct sumoylation substrate of Nse2 was not determined
    • Relevance in mammalian cells was untested
  7. 2012 High

    Identifying cohesin subunit Scc1 as a direct NSMCE2 substrate whose sumoylation promotes SUMO accumulation at DSBs, facilitates sister chromatid HR, and counteracts Wapl provided a mechanistic link between NSMCE2 and the cohesin-dependent repair pathway.

    Evidence In vitro sumoylation, non-sumoylatable Scc1-15KR mutant, live-cell imaging, Wapl epistasis

    PMID:22751501

    Open questions at the time
    • Whether sumoylation of Scc1 is the sole mechanism by which NSMCE2 promotes sister chromatid HR was unclear
    • SUMO chain type specificity was not resolved
  8. 2014 High

    Discovery that compound heterozygous NSMCE2 mutations cause primordial dwarfism with insulin resistance in humans — with nuclear defects rescued by wild-type but not ligase-dead NSMCE2 — established NSMCE2 as a disease gene and confirmed that its SUMO ligase activity is essential for replication stress recovery in patient cells.

    Evidence Patient cell analysis, micronucleus/nucleoplasmic bridge scoring, DNA fiber assay, WT vs. ligase-dead rescue, zebrafish knockdown

    PMID:25105364

    Open questions at the time
    • How the specific mutations affect protein stability vs. catalysis was incompletely characterized
    • Whether insulin resistance is a direct consequence of genomic instability was unclear
  9. 2015 High

    Two key regulatory inputs were identified: ATP binding to Smc5 allosterically activates Nse2 ligase activity (communicated through a coiled-coil disruption), and Mec1-dependent phosphorylation of Mms21 at S260/S261 positively regulates ligase output during S-phase, linking checkpoint signaling to SUMO conjugation.

    Evidence In vitro sumoylation with ATPase mutants, scanning force microscopy, phospho-site MS, phosphoablative mutant analysis in budding yeast

    PMID:25659338 PMID:25764370

    Open questions at the time
    • Whether human NSMCE2 is similarly phospho-regulated was not tested
    • Quantitative contribution of ATP vs. phosphorylation inputs was not dissected
  10. 2015 High

    Conditional knockout of NSMCE2 in adult mice produced cancer predisposition, accelerated aging, increased SCEs, and micronuclei; synthetic lethality with BLM deletion indicated BLM-independent functions in limiting recombination and ensuring chromosome segregation.

    Evidence Conditional KO mice, SCE and micronucleus assays, co-deletion epistasis with BLM in B lymphocytes

    PMID:26443207

    Open questions at the time
    • Which NSMCE2 substrates are responsible for the tumor-suppressive function was unknown
    • Whether cancer predisposition depends on SUMO ligase activity specifically was not tested
  11. 2016 High

    Demonstrating that Mms21-dependent poly- vs. mono-SUMOylation directs DSBs to distinct nuclear compartments (nuclear pores via Slx5/Slx8 vs. the nuclear envelope SUN domain Mps3) revealed that NSMCE2 controls the spatial organization of DNA repair.

    Evidence High-resolution live imaging of DSB relocation, SUMO mutant and epistasis analysis in budding yeast

    PMID:27056668

    Open questions at the time
    • Whether mammalian DSB relocation similarly depends on NSMCE2-mediated sumoylation was untested
    • Identity of mono-SUMO vs. poly-SUMO substrates at DSBs was not fully resolved
  12. 2018 High

    Showing that DNA binding to a positively charged patch in the Smc5 ARM domain directly stimulates Nse2 E3 activity provided a DNA-sensing mechanism that explains how the SMC5/6 complex activates sumoylation specifically at sites of DNA engagement.

    Evidence Biochemical sumoylation assay with ARM domain mutants, DNA damage sensitivity assays in yeast

    PMID:29769404

    Open questions at the time
    • Whether the DNA-sensing mechanism operates in the context of the full pentameric SMC5/6 complex was not shown
    • How ARM-domain sensing integrates with ATP-dependent activation was unclear
  13. 2019 High

    Demonstrating that NSMCE2 is required for rescue of collapsed replication forks by converging forks — with loss causing excess RAD51 accumulation, failure to recruit BLM, and carry-over of unrescued forks into mitosis — defined the specific replication rescue step that requires NSMCE2 in human cells.

    Evidence NSMCE2-deficient human cells, DNA fiber assay, immunofluorescence for RAD51/BLM, mitotic damage scoring, SCE assay

    PMID:30735491

    Open questions at the time
    • Which NSMCE2 substrate(s) mediate RAD51 removal at collapsed forks was unknown
    • Whether SUMO ligase activity specifically is required for this step was not directly tested
  14. 2021 High

    The crystal structure of Nse2 bound to an E2–SUMO thioester mimetic revealed that two SIM-like motifs in Nse2 are restructured upon SUMO engagement to promote thioester discharge, providing the first atomic-resolution view of the catalytic mechanism.

    Evidence X-ray crystallography of E2–SUMO thioester mimetic complex, mutagenesis and DNA damage sensitivity assays in yeast

    PMID:34853311

    Open questions at the time
    • Structure of the full Smc5–Nse2–E2–SUMO complex on DNA was not obtained
    • Whether SIM-dependent regulation differs for different substrates was unknown
  15. 2026 Medium

    Genetic dissection of the Mms21 C-terminus revealed that the last 22 residues — analogous to a region lost in a human disease mutation — contribute to genome integrity through both SUMO ligase-dependent and ligase-independent mechanisms, indicating NSMCE2 possesses functions beyond catalysis.

    Evidence Yeast truncation mutants, growth/damage sensitivity assays, cell cycle analysis, comparison with SP-RING mutations

    PMID:41949878

    Open questions at the time
    • Nature of the ligase-independent C-terminal function is unknown
    • Whether the human disease truncation phenocopies the yeast allele was not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include the identity of the full NSMCE2 substrate repertoire in human cells, the structural basis for allosteric integration of ATP, DNA, and phosphorylation inputs in the intact SMC5/6 holocomplex, and whether ligase-independent functions contribute to the human disease phenotype.
  • No proteome-wide SUMO substrate analysis in human cells attributable to NSMCE2
  • No cryo-EM or crystal structure of the full SMC5/6 holocomplex with DNA and E2–SUMO
  • Mechanism by which NSMCE2 loss causes insulin resistance is unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 7 GO:0016740 transferase activity 4 GO:0140096 catalytic activity, acting on a protein 4
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 3
Pathway
R-HSA-73894 DNA Repair 7 R-HSA-392499 Metabolism of proteins 5 R-HSA-69306 DNA Replication 4 R-HSA-1640170 Cell Cycle 3
Partners
BLMPPARASCC1SMC5SMC6TOP2AUBC9
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 decreases DNA repair capacity, effects rescued by wild-type but not ligase-inactive hMMS21 In vitro sumoylation assay, RNAi knockdown, comet assay, rescue with ligase-inactive mutant Molecular and cellular biology High 16055714
2005 Fission yeast Nse2 (ortholog of NSMCE2) is a SUMO E3 ligase within the Smc5-6 complex; it sumoylates Smc6 and Nse3 in vitro in an Nse2-dependent manner, and RING-finger mutations (C195S-H197A) abolish sumoylation activity; Nse2-dependent sumoylation is required for DNA damage response but not for the essential function of the Smc5-6 complex In vitro sumoylation assay, site-directed mutagenesis, in vivo sumoylation assay, DNA damage sensitivity assays Molecular and cellular biology High 15601841
2003 Fission yeast Nse2 co-precipitates with Smc5 as part of the Smc5-6 complex, is essential for viability, and is required for homologous recombination-based DNA double-strand break repair (epistasis with Rhp51/Rad51) Mass spectrometry of co-precipitated proteins, genetic epistasis analysis, DNA damage sensitivity assays The Journal of biological chemistry High 12966087
2006 Yeast Mms21 SUMO ligase (ortholog of NSMCE2) acts together with Ubc9 and Sgs1/BLM to resolve cruciform (X) structures that accumulate at damaged replication forks; mms21 mutants phenocopy ubc9 mutants and show Rad51-dependent accumulation of cruciform structures, distinct from the Siz1/Srs2/PCNA sumoylation pathway Genetic epistasis, two-dimensional gel electrophoresis to detect replication intermediates, mutation analysis Cell High 17081974
2009 Crystal structure of yeast Mms21 in complex with the Smc5 arm revealed two functional domains: an N-terminal helix bundle mediating Smc5 binding via coiled-coil interaction, and a C-terminal SP-RING SUMO E3 ligase domain conferring specificity to the SUMO E2-E3 interaction; mutagenesis showed the Mms21-Smc5 interface is required for cell growth and DNA damage resistance X-ray crystallography, site-directed mutagenesis, yeast growth and DNA damage assays Molecular cell High 19748359
2012 Mms21/NSMCE2 sumoylates multiple lysines on the cohesin subunit Scc1; this sumoylation promotes SUMO accumulation at DNA damage sites, facilitates sister chromatid homologous recombination, and counteracts the negative cohesin regulator Wapl at DSBs In vitro sumoylation assay, laser-induced DNA damage with live imaging, non-sumoylatable Scc1 mutant (15KR), Wapl depletion epistasis Genes & development High 22751501
2015 NSMCE2 deletion in adult mice causes cancer predisposition and accelerated aging resembling Bloom syndrome; NSMCE2-deficient cells show increased recombination rates and micronuclei accumulation; BLM and NSMCE2 foci do not colocalize and concomitant deletion is synthetic lethal, indicating BLM-independent functions of NSMCE2 in limiting recombination and facilitating chromosome segregation Conditional knockout mice, immunofluorescence, SCE assay, micronucleus assay, co-deletion epistasis in B lymphocytes The EMBO journal High 26443207
2014 Compound heterozygous frameshift mutations in NSMCE2 cause primordial dwarfism with extreme insulin resistance in humans; patient cells show increased micronuclei and 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-dead mutant, establishing the SUMO ligase activity as essential for replication stress recovery Patient cell analysis, micronucleus assay, nucleoplasmic bridge scoring, DNA fiber assay, rescue with WT vs. ligase-inactive NSMCE2, zebrafish knockdown model The Journal of clinical investigation High 25105364
2018 DNA binding directly stimulates Nse2/Mms21 SUMO E3 ligase activity; the electrostatic interaction between DNA and a positively charged patch in the ARM domain of Smc5 acts as a DNA sensor that promotes activation of Nse2 E3 activity; disruption of this ARM-DNA interaction sensitizes cells to DNA damage Biochemical sumoylation assay, mutagenesis of ARM domain, DNA damage sensitivity assays The EMBO journal High 29769404
2015 Mms21/NSMCE2 SUMO ligase activity requires docking to an intact, ATPase-active Smc5/6 complex; ATP binding to Smc5 is required for Mms21-dependent sumoylation; a conserved disruption in the Smc5 coiled-coil domain enables communication between the nucleotide-binding domain and the E3 ligase; scanning force microscopy shows ATP-dependent physical remodeling of the Smc5-Mms21 heterodimer In vitro sumoylation assay, ATPase mutants, scanning force microscopy, chromosome disjunction assays PLoS biology High 25764370
2021 Crystal structure of yeast Nse2 in complex with an E2-SUMO thioester mimetic reveals that two SIM (SUMO-interacting motif)-like motifs in Nse2 are restructured upon binding donor SUMO and E2-backside SUMO; both SIM interfaces are essential for Nse2 E3 ligase activity and DNA damage tolerance X-ray crystallography of E2-SUMO thioester mimetic complex, mutagenesis, DNA damage sensitivity assays Nature communications High 34853311
2019 NSMCE2 is required for the rescue of collapsed replication forks by converging forks in human cells; NSMCE2-deficient cells accumulate excess RAD51 at collapsed forks, fail to recruit BLM, exhibit reduced sister chromatid exchange, and carry unrescued forks into mitosis causing mitotic DNA damage NSMCE2-deficient human cells, DNA fiber assay, immunofluorescence for RAD51 and BLM, mitotic DNA damage scoring, SCE assay, double-deficiency with BLM PLoS genetics High 30735491
2016 In budding yeast, polySUMOylation by Mms21 (coordinated with Siz2) at DNA double-strand breaks drives DSB relocation to nuclear pores via the STUbL Slx5/Slx8; in S-phase, monoSUMOylation by the Rtt107-stabilized SMC5/6-Mms21 complex directs DSBs to the SUN domain protein Mps3 independently of Slx5 High-resolution live imaging of DSB relocation, SUMO mutant analysis, epistasis with Slx5/Slx8 and Mps3 Genes & development High 27056668
2009 Ablation of MMS21 (NSMCE2) in human cells leads to premature sister chromatid separation prior to anaphase, spindle assembly checkpoint activation, and mitotic arrest; mitotic SMC5 co-elutes with MMS21 in fractions lacking SMC6, suggesting a mitotic role partially independent of the full SMC5/6 complex siRNA knockdown, chromosome spreading, spindle checkpoint analysis, gel filtration chromatography Cell cycle Medium 19502785
2012 In chicken DT40 cells, SUMO ligase activity of Nse2 is required for efficient repair of bulky DNA lesions and homologous recombination, but not for Smc5/6 complex stability; Nse2 deficiency destabilizes Smc5 but not Smc6 Nse2-deficient DT40 KO cells, rescue with SUMO ligase-inactive mutant, DNA damage sensitivity assays, gel filtration DNA repair Medium 22921571
2015 Yeast Mms21 is phosphorylated by the DNA damage kinase Mec1 at serines S260 and S261 during S-phase; phosphoablative substitutions reduce SUMO ligase activity, increase MMS sensitivity, and increase chromosome loss, indicating Mec1-dependent phosphorylation positively regulates Mms21 SUMO ligase activity Mass spectrometry phospho-site identification, non-phosphorylatable mutants, SUMO ligase activity assay, chromosome loss assay DNA repair Medium 25659338
2014 Mammalian Nse2/Mms21 binds to skNAC and sumoylates its interaction partner Smyd1 in muscle cells; knockdown of Nse2 inhibits myogenic differentiation, blocks nuclear-to-cytoplasmic translocation of the skNAC-Smyd1 complex, and causes retention in PML-like nuclear bodies Co-immunoprecipitation, siRNA knockdown, immunofluorescence, differentiation assays Journal of cell science Medium 25002400
2016 CRISPR-mediated removal of NSMCE2 in human U2OS cells increases sensitivity to etoposide (topoisomerase II inhibitor) but not to ionizing radiation; immunoprecipitation/mass spectrometry shows the SMC5/6 complex physically interacts with DNA topoisomerase IIα (TOP2A), suggesting NSMCE2 functions in resolving TOP2A-mediated DSB repair intermediates during replication CRISPR-Cas9 KO, DNA damage sensitivity assays, Co-IP/mass spectrometry International journal of molecular sciences Medium 27792189
2011 Fission yeast Nse2 SUMO ligase activity is required for suppression of spontaneous Top1-mediated DNA damage (Top1 cleavage complexes); loss of Nse2 ligase activity elevates Top1cc levels (measured by ChIP-qPCR), causes hyper-recombination and checkpoint arrest; epistasis places Nse2 in the Rad16-Swi10 NER pathway parallel to Tdp1 ChIP-qPCR for Top1cc, genetic epistasis analysis, recombination assays, checkpoint analysis PLoS genetics Medium 21408210
2025 NSMCE2 promotes hepatocellular carcinoma by SUMOylating PPARα, thereby reducing PPARα ubiquitination and degradation and activating the PPARα-CYP7A1 axis; the interaction between NSMCE2 and PPARα was confirmed by co-immunoprecipitation Co-immunoprecipitation, SUMOylation assay, in vitro and in vivo tumor assays International immunopharmacology Medium 40318278
2021 In budding yeast, Esc2 (a protein with SUMO-like domains) recruits Ubc9 to specifically facilitate Mms21-dependent sumoylation; proteome-wide SUMO analysis shows Esc2-D430R mutation specifically down-regulates sumoylation of Mms21-preferred substrates including nucleolar proteins, SMC complex components, and MCM helicase subunits Quantitative proteome-wide SUMOylation mass spectrometry, co-IP, genetic epistasis PloS one Medium 33600463
2026 The C-terminus of yeast Mms21 contributes to both SUMO ligase-dependent and ligase-independent functions; truncation of the last 22 amino acids (mms21Δ22, analogous to a human NSMCE2 disease mutation) causes slower growth, DNA damage sensitivity, and G2/M delay beyond what is observed with SUMO ligase domain mutations alone, indicating the C-terminus fine-tunes genome integrity through additional mechanisms Yeast genetics, growth assays, DNA damage sensitivity, cell cycle analysis, mutant complementation Molecular biology of the cell Medium 41949878

Source papers

Stage 0 corpus · 49 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 204 16055714
2005 Nse2, a component of the Smc5-6 complex, is a SUMO ligase required for the response to DNA damage. Molecular and cellular biology 194 15601841
2009 The Arabidopsis SUMO E3 ligase AtMMS21, a homologue of NSE2/MMS21, regulates cell proliferation in the root. The Plant journal : for cell and molecular biology 129 19682286
2016 PolySUMOylation by Siz2 and Mms21 triggers relocation of DNA breaks to nuclear pores through the Slx5/Slx8 STUbL. Genes & development 103 27056668
2003 Novel essential DNA repair proteins Nse1 and Nse2 are subunits of the fission yeast Smc5-Smc6 complex. The Journal of biological chemistry 101 12966087
2004 Nse1, Nse2, and a novel subunit of the Smc5-Smc6 complex, Nse3, play a crucial role in meiosis. Molecular biology of the cell 98 15331764
2014 Hypomorphism in human NSMCE2 linked to primordial dwarfism and insulin resistance. The Journal of clinical investigation 83 25105364
2009 Structural and functional insights into the roles of the Mms21 subunit of the Smc5/6 complex. Molecular cell 75 19748359
2012 Scc1 sumoylation by Mms21 promotes sister chromatid recombination through counteracting Wapl. Genes & development 74 22751501
2012 MMS21/HPY2 and SIZ1, two Arabidopsis SUMO E3 ligases, have distinct functions in development. PloS one 67 23056518
2013 Smc5/6-Mms21 prevents and eliminates inappropriate recombination intermediates in meiosis. PLoS genetics 62 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
2011 SUMO-targeted ubiquitin ligase, Rad60, and Nse2 SUMO ligase suppress spontaneous Top1-mediated DNA damage and genome instability. PLoS genetics 44 21408210
2018 DNA activates the Nse2/Mms21 SUMO E3 ligase in the Smc5/6 complex. The EMBO journal 43 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 35 25764370
2009 SMC5 and MMS21 are required for chromosome cohesion and mitotic progression. Cell cycle (Georgetown, Tex.) 33 19502785
2019 Rescue of collapsed replication forks is dependent on NSMCE2 to prevent mitotic DNA damage. PLoS genetics 32 30735491
2021 Structural basis for the E3 ligase activity enhancement of yeast Nse2 by SUMO-interacting motifs. Nature communications 27 34853311
2016 Non-SMC Element 2 (NSMCE2) of the SMC5/6 Complex Helps to Resolve Topological Stress. International journal of molecular sciences 25 27792189
2014 The E3 SUMO ligase Nse2 regulates sumoylation and nuclear-to-cytoplasmic translocation of skNAC-Smyd1 in myogenesis. Journal of cell science 25 25002400
2013 A highly selective turn-on fluorescent sensor for Cu(II) based on an NSe2 chelating moiety and its application in living cell imaging. The Analyst 24 23612188
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
2023 PKL is stabilized by MMS21 to negatively regulate Arabidopsis drought tolerance through directly repressing AFL1 transcription. The New phytologist 14 37209253
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
1981 Hyper-recombination and mutator effects of the mms9-1, mms13-1, and mms21-1 mutations in Saccharomyces cerevisiae. Current genetics 6 24185997
2021 Shared and distinct roles of Esc2 and Mms21 in suppressing genome rearrangements and regulating intracellular sumoylation. PloS one 5 33600463
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