Affinage

SMC5

Structural maintenance of chromosomes protein 5 · UniProt Q8IY18

Length
1101 aa
Mass
128.8 kDa
Annotated
2026-06-10
100 papers in source corpus 53 papers cited in narrative 52 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SMC5 is the core ATPase subunit of the conserved Smc5/6 complex, an ATP-dependent DNA motor that compacts and topologically constrains DNA to safeguard genome integrity during replication and recombination (PMID:33301732, PMID:16892052). SMC5 heterodimerizes with SMC6 through a distinctive toroidal hinge whose 'latch' and 'hub' interfaces preferentially bind single-stranded DNA, an activity required for viability and DNA damage resistance (PMID:28134253), while the Smc5 monomer itself binds ssDNA and uses ATP to regulate DNA association (PMID:21293191). Within the assembled holocomplex the kleisin Nse4 bridges the Smc5 and Smc6 head ATPase domains and, together with Nse1/Nse3, forms a positively charged DNA clamp that captures dsDNA non-specifically (PMID:35648833, PMID:17005570); the Nse1/Nse3/Nse4 module contributes its own dsDNA-binding surface needed for chromatin association in vivo (PMID:26446992). ATP hydrolysis by the holocomplex is DNA-stimulated and is held in check by the Nse5/6 subcomplex, which anchors the ATPase heads in a non-productive state and inhibits the dimerization required to initiate DNA-loop extrusion (PMID:34191293, PMID:33849072). Functionally, Smc5/6 is a symmetric DNA loop-extruding and compaction machine that preferentially recognizes positively supercoiled and catenated DNA, locking plectonemes and linking supercoiled chromosomal regions in cis (PMID:37076626, PMID:38295804, PMID:33301732). The complex anchors the Nse2/Mms21 SUMO E3 ligase on the Smc5 arm; Nse2 activity is directly stimulated by DNA binding to a positively charged ARM patch on Smc5 that acts as a DNA sensor (PMID:19748359, PMID:29769404). Through this SUMOylation output and its DNA-compaction activity, Smc5/6 is recruited to DNA double-strand breaks where it promotes error-free sister-chromatid homologous recombination and cohesin loading, resolves recombination intermediates via SUMOylation of the Sgs1-Top3-Rmi1 dissolution complex, and maintains rDNA and telomere stability (PMID:16810316, PMID:16892052, PMID:27373152, PMID:27298337, PMID:17589526). Its essential function is interphase-specific, ensuring completion of DNA replication through difficult late-replicating and barrier-stalled regions before mitosis (PMID:26698660, PMID:32320646). Beyond chromosome maintenance, Smc5/6 acts as an intrinsic antiviral restriction factor that topologically entraps and transcriptionally silences extrachromosomal/episomal and unintegrated viral DNA through an ATPase- and SUMOylation-dependent chromatin-compaction mechanism, which diverse viral proteins (HBx, BNRF1, KSHV RTA) counteract by hijacking ubiquitin ligases to degrade the complex (PMID:26983541, PMID:27626656, PMID:33811831, PMID:36376394, PMID:36097294, PMID:35914008). Biallelic mutations in SMC5 and its complex partners cause autosomal recessive chromosome-instability syndromes characterized by chromosome breakage, replication stress, and defective homologous recombination (PMID:27427983, PMID:36333305).

Mechanistic history

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

    Establishing that Smc5 is the catalytic centerpiece of a defined multi-subunit complex was the founding step, identifying its non-SMC partners and placing them in the homologous recombination pathway.

    Evidence Protein purification with MS identification of Nse1/Nse2 and genetic epistasis in fission yeast

    PMID:12966087

    Open questions at the time
    • Did not define subunit architecture or DNA-binding mechanism
    • Catalytic activities of the complex unresolved
  2. 2005 High

    Defining the Smc5-Smc6 hinge heterodimerization interface and the embedded Nse2 SUMO ligase activity converted a genetic complex into a biochemical entity with an enzymatic output for the DNA damage response.

    Evidence Protein purification, hinge mutagenesis, and in vitro/in vivo SUMOylation assays in yeast

    PMID:15601840 PMID:15601841

    Open questions at the time
    • SUMO substrates relevant in vivo not fully enumerated
    • Structural basis of ligase specificity unresolved
  3. 2006 High

    Localization and recruitment studies established the complex acts directly at DNA double-strand breaks to drive error-free sister-chromatid recombination, distinguishing its role from other repair pathways.

    Evidence ChIP showing de novo recruitment to DSBs, HR subpathway assays, and 2D gels in human and yeast cells

    PMID:16793545 PMID:16810316 PMID:16892052

    Open questions at the time
    • Molecular signal for recruitment not defined
    • How the complex enforces sister-chromatid template choice unknown
  4. 2006 Medium

    Mapping the kleisin Nse4 and the Nse subcomplexes to the Smc5/Smc6 heads defined the modular architecture that bridges the ATPase domains.

    Evidence Y2H, co-IP, and in vitro binding assays in yeast

    PMID:17005570 PMID:19141609

    Open questions at the time
    • Single-lab interaction mapping without structural confirmation at the time
    • Functional consequences of each bridging contact not dissected
  5. 2009 High

    A crystal structure of the Mms21/Nse2-Smc5 arm interface revealed a novel RING E3 architecture and showed the interface itself is required for growth and damage resistance, anchoring the SUMO ligase on the SMC5 scaffold.

    Evidence X-ray crystallography with mutagenesis and in vitro SUMO ligase assays

    PMID:19748359

    Open questions at the time
    • How DNA context regulates the ligase not yet defined
    • Full substrate spectrum unknown
  6. 2010 Medium

    Linking Smc5/6/Mms21 to active dissolution of DNA-mediated sister-chromatid linkages before mitosis explained why complex loss causes anaphase missegregation.

    Evidence Conditional genetics with chromosome-segregation microscopy and metaphase rescue in yeast

    PMID:20571088

    Open questions at the time
    • Biochemical nature of dissolved linkages not fully defined
    • Direct enzymatic step on the linkage not shown
  7. 2015 Medium

    Reconstitution showed the purified complex binds and entraps DNA in an ATP-dependent manner, recognizing single-stranded and supercoiled/catenated substrates, providing the first direct biochemical activity for SMC5.

    Evidence In vitro DNA binding/catenation assays, ATPase mutants, and purified Smc5 ssDNA binding

    PMID:21293191 PMID:26299966 PMID:26446992

    Open questions at the time
    • Loop-extrusion behavior not yet demonstrated
    • Coupling of ATP cycle to topology change not resolved
  8. 2017 High

    The toroidal Smc5/6 hinge with its unique latch and hub interfaces was shown to bind ssDNA preferentially, linking a structural feature to a DNA-substrate preference essential for viability.

    Evidence Crystal structure, ssDNA-binding assays, and mutagenesis with viability readouts in two organisms

    PMID:28134253

    Open questions at the time
    • How hinge ssDNA binding integrates with head ATPase cycle unclear
    • In vivo ssDNA intermediates engaged not directly visualized
  9. 2018 High

    Identifying the Smc5 ARM domain as a DNA sensor that electrostatically stimulates Nse2 ligase activity coupled the complex's DNA engagement directly to its SUMOylation output.

    Evidence In vitro SUMO ligase and DNA-binding assays with ARM-patch mutants and in vivo damage sensitivity

    PMID:29769404

    Open questions at the time
    • Which substrates are selected upon ARM-DNA activation in vivo not enumerated
    • Structural snapshot of the activated state lacking
  10. 2020 High

    Holocomplex reconstitution and a DNA-bound cryo-EM structure unified the complex's activities, demonstrating DNA-dependent ATPase, SUMO ligase, and ATP-driven plectoneme-locking/compaction with a defined DNA clamp.

    Evidence In vitro ATPase/SUMO/single-molecule assays, cryo-EM at 3.8 Å, and cross-linking MS in yeast and human systems

    PMID:33301731 PMID:33301732 PMID:35648833

    Open questions at the time
    • Mechanistic transition from clamping to loop extrusion not captured
    • Human-specific regulatory differences incompletely defined
  11. 2021 High

    Demonstrating that Nse5/6 inhibits the ATPase by anchoring the heads in a non-productive state established the principal mechanism that gates complex activity, relieved by closed/long DNA.

    Evidence Crystal structure of Nse5/6, ATPase assays, cysteine and cross-linking MS, and integrative cryo-EM modeling

    PMID:33849072 PMID:33941673 PMID:34191293

    Open questions at the time
    • Cellular signals that relieve Nse5/6 inhibition not defined
    • How regulation differs across recruitment pathways unclear
  12. 2023 High

    Single-molecule imaging resolved the core mechanism: Smc5/6 dimers extrude DNA loops symmetrically and monomers translocate, with Nse5/6 blocking dimerization to control loop-extrusion initiation.

    Evidence Single-molecule imaging of reconstituted Smc5/6, with monomer/dimer and Nse5/6 dissection

    PMID:37076626

    Open questions at the time
    • In vivo relevance of loop extrusion to repair not directly tested
    • Connection to SUMOylation output during extrusion unknown
  13. 2024 High

    Coupling loop extrusion to substrate preference, Smc5/6 was shown to recognize tips of positively supercoiled plectonemes at transcription-induced cohesin-loop boundaries and gather them in cis.

    Evidence Single-molecule imaging, ChIP-seq, and Hi-C

    PMID:38295804

    Open questions at the time
    • Functional outcome of supercoil gathering for repair/replication not fully resolved
    • Interplay with cohesin at boundaries mechanistically open
  14. 2022 High

    Recognition that the chromatin-compaction and SUMOylation machinery is repurposed as an antiviral restriction factor extended SMC5/6 biology, with SLF2/SIMC1-dependent recruitment to viral DNA at PML bodies and SUMO-dependent silencing.

    Evidence CRISPR screens, ATAC-seq, NSMCE2 SUMO-mutant and inhibitor latency assays, ChIP, and structural/IP analyses of SLF2/SIMC1 in HIV-1, KSHV, EBV and polyomavirus systems

    PMID:33811831 PMID:35263599 PMID:35914008 PMID:36097294 PMID:36373674 PMID:36376394

    Open questions at the time
    • Why episomal/viral DNA is selectively recognized versus host chromatin not fully resolved
    • Relative contributions of entrapment vs SUMOylation across viruses differ and are unsettled
  15. 2022 Medium

    Human genetics confirmed the physiological essentiality of SMC5 and its partners by linking biallelic mutations to chromosome-instability syndromes with replication stress and HR defects.

    Evidence Whole exome sequencing with patient-cell HR, cohesion, and replication-stress assays for SMC5/SLF2 and NSMCE3

    PMID:27427983 PMID:36333305

    Open questions at the time
    • Genotype–phenotype relationships across the complex incompletely defined
    • Tissue-specific developmental requirements not fully explained

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the ATP-driven loop-extrusion/compaction cycle is mechanistically coupled to Nse2/Mms21 SUMOylation choices and to substrate-specific outcomes (sister-chromatid HR versus viral silencing versus replication completion) remains unresolved.
  • No structural snapshot links an extruding state to active SUMO transfer
  • Determinants directing the complex to distinct cellular versus viral substrates undefined
  • How recruitment pathways tune the Nse5/6 inhibitory switch in vivo unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 5 GO:0003677 DNA binding 4 GO:0016740 transferase activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0005198 structural molecule activity 2 GO:0140313 molecular sequestering activity 2
Localization
GO:0005694 chromosome 4 GO:0005634 nucleus 3 GO:0005730 nucleolus 3
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-168256 Immune System 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-69306 DNA Replication 4 R-HSA-73894 DNA Repair 4
Partners
MPH1NSE2/MMS21NSE3NSE4SIMC1SLF2SMC6TOP2A
Complex memberships
Smc5/6 complex

Evidence

Reading pass · 52 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2023 Smc5/6 is a DNA loop-extruding motor: single-molecule imaging demonstrated that Smc5/6 extrudes DNA loops symmetrically upon ATP hydrolysis at ~1 kb/s in a force-dependent manner. Monomeric Smc5/6 unidirectionally translocates along DNA, while dimeric Smc5/6 extrudes loops. The Nse5/6 subcomplex acts as a negative regulator of loop extrusion by inhibiting Smc5/6 dimerization, thereby preventing loop-extrusion initiation but not ongoing loop extrusion. Single-molecule imaging, in vitro reconstitution Nature High 37076626
2024 Smc5/6 associates with transcription-induced positively supercoiled DNA at cohesin-dependent loop boundaries. Single-molecule imaging showed that Smc5/6 dimers specifically recognize the tips of positively supercoiled DNA plectonemes and initiate loop extrusion to gather supercoiled DNA into large plectonemic loops. Hi-C analysis showed that Smc5/6 links chromosomal regions containing transcription-induced positive supercoiling in cis. Single-molecule imaging, ChIP-seq, Hi-C Molecular cell High 38295804
2022 Cryo-EM structure (3.8 Å) of DNA-bound yeast Smc5/6 revealed a DNA clamp formed by Smc5, Smc6, Nse1, Nse3, and Nse4. The positively charged inner surface of the clamp contacts dsDNA in a nonsequence-specific manner. The Nse3 subunit secures DNA from above; the hook-shaped Nse4 kleisin forms a scaffold connecting DNA to all other subunits. Cross-linking MS identified multi-subunit conformational changes from DNA-free to DNA-bound state enabling DNA capture. Cryo-EM structure, cross-linking mass spectrometry, mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 35648833
2016 HBx hijacks the cellular DDB1-CUL4 E3 ubiquitin ligase to target the Smc5/6 complex for ubiquitin-mediated proteasomal degradation, relieving Smc5/6-mediated transcriptional repression of extrachromosomal (cccDNA) templates. Smc5/6 associates directly with extrachromosomal DNA and the HBV genome. Silencing Smc5/6 enhances extrachromosomal reporter transcription and rescues HBx-deficient HBV replication. RNAi knockdown, reporter assays, Co-immunoprecipitation, substrate-trapping proteomics Nature High 26983541 27626656
2007 The SMC5/6 complex localizes to ALT-associated PML bodies (APBs) in ALT cancer cells and is required for targeting telomeres to APBs. The MMS21 SUMO ligase subunit of SMC5/6 SUMOylates multiple telomere-binding proteins, including TRF1 and TRF2. Inhibition of TRF1 or TRF2 SUMOylation prevents APB formation. Depletion of SMC5/6 subunits by RNAi inhibits telomere HR, causing telomere shortening and senescence in ALT cells. RNAi, co-immunoprecipitation, in vitro SUMOylation assay, immunofluorescence Nature structural & molecular biology High 17589526
2006 Human SMC5/6 complex is recruited to nuclease-induced DNA double-strand breaks and is required for recruitment of cohesin (SMC1/3) to DSBs. RNAi knockdown of SMC5/6 specifically decreases sister chromatid HR without affecting NHEJ, intra-chromatid HR, or extrachromosomal HR. RNAi, chromatin immunoprecipitation, gene targeting assays The EMBO journal High 16810316
2009 Crystal structure of Mms21 (NSE2/Nse2) in complex with the Smc5 arm revealed two functional domains: an N-terminal half forming a helix bundle with a coiled-coil region of Smc5 (required for Smc5 binding), and a C-terminal SUMO ligase domain with a new type of RING E3 structure that confers specificity to SUMO E2-E3 interaction. The Mms21-Smc5 interface is required for cell growth and DNA damage resistance. X-ray crystallography, mutagenesis, in vitro SUMO ligase assay Molecular cell High 19748359
2005 Nse2 (fission yeast SMC5/6 subunit) is a SUMO ligase: it sumoylates Smc6 and Nse3 in vitro in an Nse2-dependent manner, and autosumoylates itself. Mutations in the RING-finger-like motif (C195S/H197A) abolish Nse2-dependent sumoylation. Smc6 is sumoylated in vivo, with increased levels upon DNA damage, which is drastically reduced in nse2.SA cells. nse2.SA cells are sensitive to DNA-damaging agents, implicating Nse2 SUMO ligase activity in DNA damage responses. In vitro sumoylation assay, mutagenesis, in vivo sumoylation analysis, DNA damage sensitivity assays Molecular and cellular biology High 15601841
2006 Nse4 is the kleisin component of the Smc5/6 complex, bridging the heads of Smc5 and Smc6. The C-terminal part of Nse4 interacts with the head domain of Smc5; specific mutations in a predicted winged helix motif of Nse4 destroy this interaction. Nse3, Nse5, and Nse6 also bridge the Smc5 and Smc6 heads at different sites. The Nse1-Nse3-Nse4 and Nse5-Nse6 subcomplexes bind to the Smc5-Smc6 heads domain at different sites. Co-immunoprecipitation, yeast two-hybrid, in vitro binding assays, structural predictions The Journal of biological chemistry Medium 17005570
2005 Human and S. pombe Smc5 and Smc6 interact through their hinge domains. Temperature-sensitive mutations in Rad18 (Smc6) all map to the same conserved glycine in the hinge region, and this mutation abolishes hinge-hinge interaction between Smc6 and Smc5. Two subcomplexes were identified: Rad18-Spr18-Nse2 and Nse1-Nse3-Rad62. Protein purification, co-immunoprecipitation, mutagenesis, mass spectrometry Molecular and cellular biology Medium 15601840
2009 The architecture of the budding yeast Smc5/6 complex shows Smc5 and Smc6 associating at their hinge regions; Nse1-Nse3-Nse4 form a subcomplex binding the Smc5 head and adjacent coiled-coil; Nse2 binds the middle of the Smc5 coiled-coil; Nse5-Nse6 form a heterodimer that binds the hinge regions of both Smc5 and Smc6. Yeast two-hybrid, in vitro binding assays with purified recombinant proteins The Journal of biological chemistry Medium 19141609
2015 Purified Smc5/6 binds DNA through a mechanism requiring ATP hydrolysis and circular DNA. This promotes topoisomerase 2-dependent catenation of plasmids, suggesting Smc5/6 interconnects two DNA molecules via ATP-regulated topological entrapment. An Smc6 mutant defective in ATP binding fails to interact with DNA and chromosomes and causes cell death with DNA damage accumulation when overexpressed. In vitro DNA binding assay with purified complex, plasmid catenation assay, ATPase mutant analysis Cell reports Medium 26299966
2020 Purified budding yeast Smc5/6 holocomplex exhibits DNA-dependent ATP hydrolysis, SUMO E3 ligase activity, and topological DNA binding with affinity for supercoiled and catenated DNA. Single-molecule assays showed that Smc5/6 locks DNA plectonemes and compacts DNA in an ATP-dependent manner. In vitro ATPase assay, SUMO E3 ligase assay, DNA binding assay, single-molecule imaging Molecular cell High 33301732
2020 The human Smc5/6 complex recognizes unusual DNA configurations (non-B DNA) and uses ATP hydrolysis to compact DNA. Structural analyses revealed subunit interfaces responsible for functionality; mutations in these interfaces lead to chromosome breakage syndromes in humans. In vitro DNA compaction assay, structural analysis, mutagenesis Molecular cell Medium 33301731
2021 The Nse5/6 sub-complex strongly inhibits Smc5/6 ATPase by preventing productive ATP binding. This inhibition is relieved by plasmid DNA but not by short linear DNA. Two binding sites for Nse5/6 on Smc5/6 were identified: one at the Smc5/6 arms and one at the heads (exerting inhibitory effects). Nse4/3/1 module detaches from the ATPase domains under ATP and DNA conditions. Cysteine cross-linking demonstrated Nse5/6 anchors the ATPase domains in a non-productive state destabilized by ATP and DNA. In vitro ATPase assay, crystal structure of Nse5/6, cross-linking mass spectrometry, cysteine cross-linking The EMBO journal High 34191293
2021 Nse5/6 acts as a negative regulator of Smc5/6 ATPase activity by binding to the head-end of the complex to suppress ATP turnover. Only the six-protein holo-complex is capable of hydrolyzing ATP; ATPase activity is significantly increased by double-stranded DNA. ATPase stimulation requires functional ATP-binding pockets in both Smc5 and Smc6. In vitro ATPase assay with reconstituted Smc5/6 complexes, negative-stain electron microscopy Nucleic acids research High 33849072
2021 Integrative structural study of yeast Smc5/6 by cryo-EM, cross-linking MS, and computational modeling revealed that Smc5 and Smc6 arms do not fold back (unlike cohesin/condensin arms). Instead, the long filamentous arm regions interact with Nse2 (SUMO ligase) and Nse5/Nse6 subcomplex. A 3.0-Å cryo-EM structure of Nse5/Nse6 revealed a clasped-hand topology and dimeric interface. Nse5/Nse6 uses SUMO-binding motifs to contribute to Nse2-mediated sumoylation. Cryo-EM, cross-linking mass spectrometry, computational modeling Proceedings of the National Academy of Sciences of the United States of America High 33941673
2018 The Nse2/Mms21 SUMO E3 ligase activity within the Smc5/6 complex is directly stimulated by DNA binding. Stimulation requires the electrostatic interaction between DNA and a positively charged patch in the ARM domain of Smc5, which acts as a DNA sensor and promotes activation of Nse2 E3 activity. Disruption of the ARM-DNA interaction sensitizes cells to DNA damage. In vitro SUMO ligase assay, mutagenesis, DNA-binding assay The EMBO journal High 29769404
2007 The Smc5-Smc6 complex and SUMO modification of Rad52 regulate recombinational repair at the rDNA locus. Recombinational repair of a DSB in rDNA involves transient relocalization of the lesion to an extranucleolar site. Nucleolar exclusion of Rad52 recombination foci requires Mre11 and Smc5-Smc6, and depends on Rad52 SUMO modification. Mutations abrogating these activities cause rDNA hyperrecombination and excision of extrachromosomal rDNA circles. Fluorescence microscopy of repair foci, genetic epistasis, sumoylation assays Nature cell biology High 17643116
2006 The Smc5-Smc6 complex is recruited de novo to DNA DSBs and promotes repair by homologous recombination between sister chromatids. Loss of Smc5-Smc6 causes accumulation of gross chromosomal rearrangements and failure of error-free sister-chromatid recombination. Chromatin immunoprecipitation, genetic analysis, 2D gel electrophoresis Nature cell biology High 16892052
2005 SMC5 and SMC6 are required for segregation of repetitive chromosomal regions. In conditional mutants, chromosome segregation of repetitive regions (rDNA, telomeres) is impaired, leading to X-shaped DNA (Holliday junctions) accumulation at rDNA loci. RAD52 deletion partially suppresses temperature sensitivity, indicating the complex prevents formation of sister chromatid junctions at repetitive loci. Conditional genetics, 2D gel electrophoresis, chromatin immunoprecipitation, genetic epistasis Nature cell biology High 15793567
2009 The Smc5/6 complex directly binds to the DNA helicase Mph1 and modulates Mph1-dependent recombination. Deletion of MPH1 or its helicase mutations suppress multiple defects in Smc5/6 mutants, while MPH1 overexpression exacerbates them. Mph1 and its helicase activity are largely responsible for accumulation of deleterious recombination intermediates in Smc5/6 mutants, defining a function of Smc5/6 distinct from Sgs1. Co-immunoprecipitation (direct binding), genetic epistasis, 2D gel analysis Proceedings of the National Academy of Sciences of the United States of America Medium 19995966
2016 Smc5/6 mediates SUMOylation of the Sgs1-Top3-Rmi1 (STR) complex. Sgs1 binds poly-SUMO chains and associates with the Smc5/6 SUMO E3 complex. Smc5/6-dependent sumoylation of Sgs1, Top3, and Rmi1 upon generation of recombination structures promotes STR inter-subunit interactions and accumulation at DNA repair centers, facilitating removal of recombination intermediates. Co-immunoprecipitation, in vivo SUMO modification assay, 2D gel electrophoresis, protein interaction assays Cell reports Medium 27373152
2016 Smc5/6 recruits and activates Sgs1 through a two-step SUMOylation mechanism: (1) auto-SUMOylation of Smc5/6 subunits leads to recruitment of the STR complex via two SUMO-interacting motifs (SIMs) on Sgs1 that recognize SUMOylated Smc5/6; (2) Smc5/6-dependent SUMOylation of Sgs1 and Top3 is required for efficient STR function. Sgs1 SIM mutants show unprocessed HJs, increased crossovers, and impaired DNA end resection. Mutagenesis of SIMs, in vivo sumoylation assays, 2D gel electrophoresis, recombination assays Genes & development Medium 27298337
2017 The Smc5/6 hinge forms a toroidal structure with distinctive interfaces ('molecular latch' and 'hub') absent from other SMC complexes. The Smc5/6 hinge binds preferentially to ssDNA; both latch and hub mutations reduce ssDNA binding and cause severe DNA damage sensitivity and reduced human cell viability. Crystal structure, mutagenesis, DNA-binding assay (ssDNA preference), cell viability assay Nature communications High 28134253
2015 The essential functions of Smc5/6 segregate to G2/M phase. Smc5/6 is specifically required in G2/M for: (1) metabolism of DNA recombination structures triggered by endogenous replication stress, cooperating with dissolution activities; (2) replication through natural pausing sites in late-replicating regions via cooperation with the fork protection complex Tof1-Csm3. Cell-cycle-regulated alleles, genetic screens, 2D gel electrophoresis Molecular cell Medium 26698660
2006 Chromosomal localization of budding yeast Smc5/6 complex occurs in three distinct, differentially regulated pathways: (1) association with centromeres and chromosome arms in unchallenged cells; (2) association with DNA breaks; (3) association with rDNA arrays. Localization to collapsed replication forks was also detected. Smc5/6 is needed during replication to prevent accumulation of branched chromosome structures. Chromatin immunoprecipitation (ChIP), 2D gel electrophoresis Molecular cell Medium 16793545
2008 Localization of fission yeast Smc5/6 to centromeres during replication requires H3-K9 methylation (heterochromatin), while MMS-induced localization to subtelomeres requires Nse2 SUMO ligase activity but not H3-K9 methylation. Smc5/6 also loads at all genomic tDNAs in a manner requiring intact TFIIIC-binding sites. ChIP-on-chip, fluorescence microscopy, mutant analysis The EMBO journal Medium 18923417
2015 The NSE1/NSE3/NSE4 sub-complex of SMC5/6 binds double-stranded DNA without sequence or structure preference. Mutations in key basic residues on the DNA-binding surface reduce DNA binding in vitro; introduction of these mutations in S. pombe leads to cell death or hypersensitivity to DNA damage. ChIP of the hypomorphic nse3 DNA-binding mutant shows reduced SMC5/6 chromatin association in vivo. In vitro DNA-binding assay, mutagenesis, chromatin immunoprecipitation Nucleic acids research Medium 26446992
2010 Dissolution of DNA-mediated sister chromatid linkages before mitosis is an active process requiring the Smc5/6 complex and its associated Mms21 SUMO ligase. Failure to remove these linkages causes gross chromosome missegregation in anaphase. Smc5/6 can dissolve these linkages in metaphase-arrested cells, restoring chromosome resolution. Genetic analysis, microscopy of chromosome segregation, cell cycle analysis Nucleic acids research Medium 20571088
2009 In fission yeast smc6 mutants following DNA damage in interphase, chromosome arm segregation fails due to aberrant persistence of cohesin normally removed by the Separase-independent pathway. This cohesin retention is independent of DNA damage per se. Separase overexpression bypasses the defect and restores cell viability. Genetic analysis, co-immunoprecipitation, cell viability assays, microscopy Molecular and cellular biology Medium 19528228
2011 In budding yeast, Rtt107/Esc4 is required for recruitment of the SMC5/6 complex to DNA double-strand breaks. The interaction between Rtt107 and SMC5/6 is mediated through the N-terminal BRCT domains of Rtt107 and the Nse6 subunit of SMC5/6, and is independent of MMS-induced damage and Slx4. Co-immunoprecipitation, chromatin immunoprecipitation at DSBs, two-hybrid analysis The Journal of biological chemistry Medium 21642432
2011 Smc5 binds strongly and specifically to single-stranded DNA (ssDNA) independent of Smc6 as a monomer. Smc5 ATPase activity is essential for its in vivo functions, and ATP regulates the association of Smc5 with DNA substrates in vitro. Smc5 binds efficiently to oligonucleotides consistent in size with ssDNA intermediates from DNA replication and repair. In vitro DNA-binding assay with purified Smc5, ATPase assay, mutagenesis Cell cycle (Georgetown, Tex.) Medium 21293191
2022 The SMC5/6 complex compacts and silences unintegrated HIV-1 DNA. SLF2 recruits the SMC5/6 complex to unintegrated lentiviruses. ATAC-seq showed that Vpr-mediated SLF2 depletion increases chromatin accessibility of unintegrated virus, demonstrating that SMC5/6 compacts viral chromatin to silence gene expression. CRISPR screen, ATAC-seq, knockdown/depletion experiments Cell host & microbe Medium 33811831
2022 Epigenetic silencing of unintegrated HIV-1 proviruses by SMC5/6 requires SUMOylation: SMC5/6 binds to and SUMOylates unintegrated chromatinized HIV-1 DNA via NSMCE2 (SUMO E3 ligase). Inhibiting SUMOylation (by NSMCE2 point mutation or TAK-981 inhibitor) prevents silencing, enables transcription from unintegrated HIV-1 DNA, and suppresses establishment of HIV-1 latency. CRISPR/Cas9 screen, point mutagenesis, SUMOylation inhibitor, HIV-1 latency assay Nature microbiology High 36376394
2022 Transcriptional silencing by human Smc5/6 is a three-step process: (1) entrapment of episomal DNA dependent on Smc5/6 ATPase activity and Nse4a (not Nse4b); (2) recruitment to PML nuclear bodies by SLF2 (human Nse6 ortholog); (3) silencing requiring Nse2 but not its SUMO ligase activity. Cohesin and condensin fail to bind or silence episomal DNA, indicating this is unique to Smc5/6. Functional assay with mutants, reporter assay, localization by immunofluorescence, domain swap experiments Nature structural & molecular biology High 36097294
2010 Smc5/6 localizes to APBs in ALT cells and is required for localization to ND10/PML bodies in primary human hepatocytes. In hepatocytes, Smc5/6 localizes with Nuclear Domain 10 (ND10); depletion of ND10 structural components alters the nuclear distribution of Smc6 and induces HBV gene expression. Immunofluorescence co-localization, siRNA depletion, reporter assay PloS one Medium 28095508
2022 EBV tegument protein BNRF1 targets SMC5/6 complexes for degradation via a ubiquitin-proteasome pathway dependent on calpain proteolysis and Cullin-7, to evade SMC5/6 restriction of viral replication compartments. In the absence of BNRF1, SMC5/6 associates with R-loop structures at the viral lytic origin of replication, interfering with replication compartment formation. Proteomics, CRISPR analysis, co-immunoprecipitation, viral replication assay Cell reports Medium 35263599
2022 KSHV RTA protein degrades the SMC5/6 complex via the ubiquitin-proteasome system to antagonize SMC5/6-induced viral chromatin compaction. SMC5/6 binds to the KSHV genome and suppresses KSHV gene transcription by condensing viral chromatin into a repressive structure. ChIP, viral gene expression assay, protein degradation assay, chromatin compaction assay PLoS pathogens Medium 35914008
2022 The human SIMC1 protein is a novel SMC5/6 subunit containing SUMO-interacting motifs (SIMs) and an Nse5-like domain. SIMC1 uses its SIMs and Nse5-like domain to localize SMC5/6 to polyomavirus replication centers at SUMO-rich PML nuclear bodies. SIMC1's Nse5-like domain binds SLF2 to form an anti-parallel helical dimer resembling yeast Nse5/6. Proteomics, co-immunoprecipitation, structural analysis, mutagenesis, localization assay eLife Medium 36373674
2016 Biallelic missense mutations in NSMCE3 (a SMC5/6 complex subunit) disrupt interactions within the SMC5/6 complex, destabilizing it. Patient cells showed chromosome rearrangements, micronuclei, sensitivity to replication stress and DNA damage, and defective homologous recombination, establishing an autosomal recessive chromosome breakage syndrome. Whole exome sequencing, protein interaction assays, cell-based HR assay, chromosome analysis The Journal of clinical investigation Medium 27427983
2022 Biallelic variants in SLF2 and SMC5 cause a chromosome instability syndrome (Atelís Syndrome) characterized by segmented and dicentric chromosomes with mosaic variegated hyperploidy. Patient-derived cells show elevated replication stress partly due to reduced ability to replicate through G-quadruplex DNA structures and loss of sister chromatid cohesion. Whole exome sequencing, cell-based replication stress assays, chromosome analysis, cohesion assay Nature communications Medium 36333305
2009 RNAi ablation of SMC5 or MMS21 (but not SMC6) leads to premature sister chromatid separation before anaphase, activating the spindle assembly checkpoint and blocking mitotic progression. Mitotic SMC5 co-elutes with MMS21 in column fractions lacking SMC6, suggesting a mitotic SMC5-MMS21 sub-complex independent of SMC5/6. RNAi, immunoprecipitation, flow cytometry, live-cell imaging Cell cycle (Georgetown, Tex.) Medium 19502785
2013 In human cells, Smc5/6 associates with chromatin during interphase but largely dissociates from chromosomes during mitotic chromosome condensation. Depletion of Smc5 and Smc6 causes aberrant mitotic chromosome phenotypes with abnormal distribution of topoisomerase IIα and condensins, and chromosome segregation errors. Smc5/6 is required for on-time progression of DNA replication and subsequent binding of topo IIα on replicated chromatids. Chromatin fractionation, immunofluorescence, live-cell imaging, premature chromosome condensation assay Molecular biology of the cell Medium 24258023
2021 SMC5/6 depletion in human cells is essential for viability; inactivation is associated with spontaneous DNA damage, p53 activation, cell-cycle arrest, and senescence. Chromosome missegregation caused by SMC5/6 impairment requires impaired SMC5/6 function during the preceding S and G2 phases; SMC5/6 degradation immediately prior to mitotic entry has little impact on chromosome segregation fidelity. Auxin-inducible degron system for acute depletion, cell viability assay, live-cell imaging, flow cytometry Cell reports Medium 32320646
2016 Smc5/6 is present at telomeres throughout the cell cycle. Its association with chromosome ends depends on Nse3 subunit. Nse3 interacts physically and genetically with Rap1-binding factors Rif2 and Sir4. Reduced telomere-associated Smc5/6 leads to defects in telomere clustering, dispersion of Sir4, and loss of transcriptional repression of subtelomeric genes and TERRA. Chromatin immunoprecipitation, co-immunoprecipitation, fluorescence microscopy, genetic analysis PLoS genetics Medium 27564449
2018 PJA1 (a RING-H2 E3 ubiquitin ligase) interacts with the SMC5/6 complex and facilitates binding of the complex to viral and episomal DNAs in the cell nucleus. Treatment with topoisomerase inhibitors and topoisomerase knockdown relieve PJA1-mediated silencing of viral and extrachromosomal DNAs. Co-immunoprecipitation, reporter assay, RNAi, inhibitor treatment Journal of virology Low 30185588
2016 NSMCE2 (NSE2/Mms21) depletion in human cells (U2OS) increases sensitivity to etoposide (topoisomerase II inhibitor) but not to ionizing radiation. Immunoprecipitation and mass spectrometry showed the SMC5/6 complex physically interacts with DNA Topoisomerase IIα (TOP2A), suggesting SMC5/6 resolves TOP2A-mediated DSB-repair intermediates during replication. CRISPR-Cas9 knockout, immunoprecipitation, mass spectrometry International journal of molecular sciences Low 27792189
2021 SMC5/6 depletion in neural progenitor cells (NPCs) leads to DNA replication stress at late-replicating regions such as pericentromeric heterochromatin, causing chromosome missegregation, DNA bridges, and NPC apoptosis. Concomitant deletion of Trp53 or Chek2 rescues Smc5 cKO neurodevelopmental defects, placing SMC5/6 in a CHEK2-p53 DNA damage response pathway. Conditional knockout, epistasis with Trp53 and Chek2, DNA fiber assay, immunofluorescence eLife Medium 33200984
2021 Single-molecule tracking in live fission yeast showed Smc5/6 is chromatin-associated in unchallenged cells. This constitutive chromatin association depends on Nse6 through at least two sub-pathways, one requiring the BRCT-domain protein Brc1. The Nse3 double-stranded DNA binding activity and the arginine fingers of both Smc5/6 ATPase sites are critical for chromatin association. Disrupting the ssDNA binding activity at the hinge region (without preventing chromatin association) leads to elevated gross chromosomal rearrangements during replication restart. Single-molecule live-cell tracking, genetic analysis with defined mutants eLife Medium 33860765
2003 Fission yeast Smc5 was purified and Nse1 and Nse2 were identified by mass spectrometry as co-precipitating non-SMC subunits that interact with Smc5 in vivo as part of the Smc5-Smc6 complex. Both are essential proteins with DNA damage repair functions epistatic to Rhp51, placing them in the homologous recombination pathway. Protein purification, mass spectrometry, co-immunoprecipitation, genetic epistasis The Journal of biological chemistry Medium 12966087
2018 In budding yeast, acute Smc5/6 depletion reveals a primary defect in replication of the rDNA array. This is linked to programmed replication fork barriers (RFBs) established by Fob1; Fob1 deletion improves rDNA replication in Smc5/6-depleted cells. Deletion of Mph1 helicase similarly reduces recombination structures at RFB regions, confirming Smc5/6 restrains Mph1-dependent recombination at protein-barrier-stalled forks. Auxin-inducible degron depletion, 2D gel electrophoresis, genetic epistasis PLoS genetics Medium 29360860

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Hepatitis B virus X protein identifies the Smc5/6 complex as a host restriction factor. Nature 448 26983541
2007 The Smc5-Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus. Nature cell biology 331 17643116
2007 The SMC5/6 complex maintains telomere length in ALT cancer cells through SUMOylation of telomere-binding proteins. Nature structural & molecular biology 312 17589526
2016 Hepatitis B Virus X Protein Promotes Degradation of SMC5/6 to Enhance HBV Replication. Cell reports 259 27626656
2006 Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks. The EMBO journal 225 16810316
2005 Nse2, a component of the Smc5-6 complex, is a SUMO ligase required for the response to DNA damage. Molecular and cellular biology 196 15601841
2006 Chromosomal association of the Smc5/6 complex reveals that it functions in differently regulated pathways. Molecular cell 170 16793545
2006 Smc5-Smc6 mediate DNA double-strand-break repair by promoting sister-chromatid recombination. Nature cell biology 161 16892052
2005 SMC5 and SMC6 genes are required for the segregation of repetitive chromosome regions. Nature cell biology 160 15793567
2017 The Smc5/6 Complex Restricts HBV when Localized to ND10 without Inducing an Innate Immune Response and Is Counteracted by the HBV X Protein Shortly after Infection. PloS one 126 28095508
2006 The Nse5-Nse6 dimer mediates DNA repair roles of the Smc5-Smc6 complex. Molecular and cellular biology 123 16478984
2018 The Smc5/6 Complex: New and Old Functions of the Enigmatic Long-Distance Relative. Annual review of genetics 114 30476445
2006 Smc5/6 is required for repair at collapsed replication forks. Molecular and cellular biology 113 17030601
2003 Novel essential DNA repair proteins Nse1 and Nse2 are subunits of the fission yeast Smc5-Smc6 complex. The Journal of biological chemistry 102 12966087
2008 Smc5/6: a link between DNA repair and unidirectional replication? Nature reviews. Molecular cell biology 101 18059412
2005 Composition and architecture of the Schizosaccharomyces pombe Rad18 (Smc5-6) complex. Molecular and cellular biology 98 15601840
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
2023 The Smc5/6 complex is a DNA loop-extruding motor. Nature 97 37076626
2015 Essential Roles of the Smc5/6 Complex in Replication through Natural Pausing Sites and Endogenous DNA Damage Tolerance. Molecular cell 97 26698660
2009 The unnamed complex: what do we know about Smc5-Smc6? Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 94 19308705
2009 The Saccharomyces cerevisiae Esc2 and Smc5-6 proteins promote sister chromatid junction-mediated intra-S repair. Molecular biology of the cell 92 19158389
2006 The Smc5-Smc6 DNA repair complex. bridging of the Smc5-Smc6 heads by the KLEISIN, Nse4, and non-Kleisin subunits. The Journal of biological chemistry 91 17005570
2009 Smc5/6 maintains stalled replication forks in a recombination-competent conformation. The EMBO journal 89 19158664
2002 Identification of a novel non-structural maintenance of chromosomes (SMC) component of the SMC5-SMC6 complex involved in DNA repair. The Journal of biological chemistry 89 11927594
2004 Coordination of DNA damage responses via the Smc5/Smc6 complex. Molecular and cellular biology 83 14701739
2009 Interplay between the Smc5/6 complex and the Mph1 helicase in recombinational repair. Proceedings of the National Academy of Sciences of the United States of America 82 19995966
2007 Identification of the proteins, including MAGEG1, that make up the human SMC5-6 protein complex. Molecular and cellular biology 80 18086888
2009 Architecture of the Smc5/6 Complex of Saccharomyces cerevisiae Reveals a Unique Interaction between the Nse5-6 Subcomplex and the Hinge Regions of Smc5 and Smc6. The Journal of biological chemistry 78 19141609
2009 Structural and functional insights into the roles of the Mms21 subunit of the Smc5/6 complex. Molecular cell 77 19748359
2021 Therapeutic shutdown of HBV transcripts promotes reappearance of the SMC5/6 complex and silencing of the viral genome in vivo. Gut 73 33509930
2016 Smc5/6 Mediated Sumoylation of the Sgs1-Top3-Rmi1 Complex Promotes Removal of Recombination Intermediates. Cell reports 72 27373152
2015 The Smc5/6 Complex Is an ATP-Dependent Intermolecular DNA Linker. Cell reports 72 26299966
2021 The SMC5/6 complex compacts and silences unintegrated HIV-1 DNA and is antagonized by Vpr. Cell host & microbe 71 33811831
2010 The Smc5/6 complex and Esc2 influence multiple replication-associated recombination processes in Saccharomyces cerevisiae. Molecular biology of the cell 70 20444977
2021 HBx-induced degradation of Smc5/6 complex impairs homologous recombination-mediated repair of damaged DNA. Journal of hepatology 69 34478763
2013 Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions. PLoS genetics 66 24385939
2010 The Smc5/6 complex is required for dissolution of DNA-mediated sister chromatid linkages. Nucleic acids research 65 20571088
2016 Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease. The Journal of clinical investigation 64 27427983
2015 Chromatin association of the SMC5/6 complex is dependent on binding of its NSE3 subunit to DNA. Nucleic acids research 64 26446992
2013 Smc5/6-Mms21 prevents and eliminates inappropriate recombination intermediates in meiosis. PLoS genetics 63 24385936
2008 Localization of Smc5/6 to centromeres and telomeres requires heterochromatin and SUMO, respectively. The EMBO journal 63 18923417
2020 Purified Smc5/6 Complex Exhibits DNA Substrate Recognition and Compaction. Molecular cell 61 33301732
2013 Smc5/6-mediated regulation of replication progression contributes to chromosome assembly during mitosis in human cells. Molecular biology of the cell 61 24258023
2020 The Smc5/6 Core Complex Is a Structure-Specific DNA Binding and Compacting Machine. Molecular cell 60 33301731
2016 Sgs1's roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6. Genes & development 60 27298337
2004 Rad62 protein functionally and physically associates with the smc5/smc6 protein complex and is required for chromosome integrity and recombination repair in fission yeast. Molecular and cellular biology 59 15485909
2017 Specialized interfaces of Smc5/6 control hinge stability and DNA association. Nature communications 56 28134253
2014 The chromosomal association of the Smc5/6 complex depends on cohesion and predicts the level of sister chromatid entanglement. PLoS genetics 54 25329383
2008 Nse1 RING-like domain supports functions of the Smc5-Smc6 holocomplex in genome stability. Molecular biology of the cell 54 18667531
2022 Epstein-Barr virus BNRF1 destabilizes SMC5/6 cohesin complexes to evade its restriction of replication compartments. Cell reports 52 35263599
2009 The Yin and Yang of the MMS21-SMC5/6 SUMO ligase complex in homologous recombination. DNA repair 48 19217832
2017 The Smc5/6 complex regulates the yeast Mph1 helicase at RNA-DNA hybrid-mediated DNA damage. PLoS genetics 47 29281624
2011 Interactions between the Nse3 and Nse4 components of the SMC5-6 complex identify evolutionarily conserved interactions between MAGE and EID Families. PloS one 47 21364888
2021 Integrative analysis reveals unique structural and functional features of the Smc5/6 complex. Proceedings of the National Academy of Sciences of the United States of America 45 33941673
2018 DNA activates the Nse2/Mms21 SUMO E3 ligase in the Smc5/6 complex. The EMBO journal 45 29769404
2011 Roles of vertebrate Smc5 in sister chromatid cohesion and homologous recombinational repair. Molecular and cellular biology 45 21245390
2021 Nse5/6 inhibits the Smc5/6 ATPase and modulates DNA substrate binding. The EMBO journal 44 34191293
2020 Inducible Degradation of the Human SMC5/6 Complex Reveals an Essential Role Only during Interphase. Cell reports 44 32320646
2006 Rhp51-dependent recombination intermediates that do not generate checkpoint signal are accumulated in Schizosaccharomyces pombe rad60 and smc5/6 mutants after release from replication arrest. Molecular and cellular biology 44 16354704
2023 The multi-functional Smc5/6 complex in genome protection and disease. Nature structural & molecular biology 43 37336994
2022 Cryo-EM structure of DNA-bound Smc5/6 reveals DNA clamping enabled by multi-subunit conformational changes. Proceedings of the National Academy of Sciences of the United States of America 43 35648833
2012 During replication stress, non-SMC element 5 (NSE5) is required for Smc5/6 protein complex functionality at stalled forks. The Journal of biological chemistry 43 22303010
2011 The Smc5/6 complex: more than repair? Cold Spring Harbor symposia on quantitative biology 43 21467147
2013 Dynamic localization of SMC5/6 complex proteins during mammalian meiosis and mitosis suggests functions in distinct chromosome processes. Journal of cell science 42 23843628
2018 SMC5/6: Multifunctional Player in Replication. Genes 41 30583551
2011 The Nse2/Mms21 SUMO ligase of the Smc5/6 complex in the maintenance of genome stability. FEBS letters 41 21550342
2009 Smc5-Smc6-dependent removal of cohesin from mitotic chromosomes. Molecular and cellular biology 41 19528228
2018 Scaffolding for Repair: Understanding Molecular Functions of the SMC5/6 Complex. Genes 39 29329249
2018 Acute Smc5/6 depletion reveals its primary role in rDNA replication by restraining recombination at fork pausing sites. PLoS genetics 39 29360860
2017 Identifying and Characterizing Interplay between Hepatitis B Virus X Protein and Smc5/6. Viruses 39 28368357
2011 Rtt107 is required for recruitment of the SMC5/6 complex to DNA double strand breaks. The Journal of biological chemistry 39 21642432
2018 Smc5/6 Antagonism by HBx Is an Evolutionarily Conserved Function of Hepatitis B Virus Infection in Mammals. Journal of virology 38 29848586
2005 Qri2/Nse4, a component of the essential Smc5/6 DNA repair complex. Molecular microbiology 38 15752197
2022 Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy. Nature communications 37 36333305
2012 Meiotic DNA joint molecule resolution depends on Nse5-Nse6 of the Smc5-Smc6 holocomplex. Nucleic acids research 37 22855558
2022 KSHV RTA antagonizes SMC5/6 complex-induced viral chromatin compaction by hijacking the ubiquitin-proteasome system. PLoS pathogens 35 35914008
2011 Dynamic and selective DNA-binding activity of Smc5, a core component of the Smc5-Smc6 complex. Cell cycle (Georgetown, Tex.) 35 21293191
2021 RAD51 supports DMC1 by inhibiting the SMC5/6 complex during meiosis. The Plant cell 34 34009315
2013 Inhibition of the Smc5/6 complex during meiosis perturbs joint molecule formation and resolution without significantly changing crossover or non-crossover levels. PLoS genetics 34 24244180
2018 The SMC5/6 Complex Interacts with the Papillomavirus E2 Protein and Influences Maintenance of Viral Episomal DNA. Journal of virology 33 29848583
2009 SMC5 and MMS21 are required for chromosome cohesion and mitotic progression. Cell cycle (Georgetown, Tex.) 33 19502785
2024 Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils. Molecular cell 32 38295804
2022 Epigenetic silencing by the SMC5/6 complex mediates HIV-1 latency. Nature microbiology 32 36376394
2020 Molecular Insights into the Architecture of the Human SMC5/6 Complex. Journal of molecular biology 32 32389690
2019 The SMC5/6 Complex Subunit NSE4A Is Involved in DNA Damage Repair and Seed Development. The Plant cell 32 31036599
2018 PJA1 Coordinates with the SMC5/6 Complex To Restrict DNA Viruses and Episomal Genes in an Interferon-Independent Manner. Journal of virology 32 30185588
2017 SMC5/6 is required for the formation of segregation-competent bivalent chromosomes during meiosis I in mouse oocytes. Development (Cambridge, England) 31 28302748
2012 The Smc5-Smc6 complex regulates recombination at centromeric regions and affects kinetochore protein sumoylation during normal growth. PloS one 31 23284708
2022 Smc5/6 silences episomal transcription by a three-step function. Nature structural & molecular biology 30 36097294
2007 Brc1-mediated rescue of Smc5/6 deficiency: requirement for multiple nucleases and a novel Rad18 function. Genetics 30 17277362
2016 Smc5/6 Is a Telomere-Associated Complex that Regulates Sir4 Binding and TPE. PLoS genetics 28 27564449
2008 Smc5-Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications. DNA repair 28 18585101
2020 SMC5/6 is required for replication fork stability and faithful chromosome segregation during neurogenesis. eLife 27 33200984
2022 The Nse5/6-like SIMC1-SLF2 complex localizes SMC5/6 to viral replication centers. eLife 26 36373674
2021 Nse5/6 is a negative regulator of the ATPase activity of the Smc5/6 complex. Nucleic acids research 26 33849072
2021 Live-cell single-molecule tracking highlights requirements for stable Smc5/6 chromatin association in vivo. eLife 26 33860765
2007 Requirement of Nse1, a subunit of the Smc5-Smc6 complex, for Rad52-dependent postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae. Molecular and cellular biology 26 17923688
2019 SMC5/6 acts jointly with Fanconi anemia factors to support DNA repair and genome stability. EMBO reports 25 31867888
2016 Non-SMC Element 2 (NSMCE2) of the SMC5/6 Complex Helps to Resolve Topological Stress. International journal of molecular sciences 25 27792189
2014 Loss of Caenorhabditis elegans BRCA1 promotes genome stability during replication in smc-5 mutants. Genetics 25 24424777

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