Gene Symbol: SMC6
Description: structural maintenance of chromosomes 6
Alias: SMC-6, SMC6L1, hSMC6, structural maintenance of chromosomes protein 6, SMC protein 6, SMC6 structural maintenance of chromosomes 6-like 1
Species: human
Products:     SMC6

Top Publications

  1. Potts P, Porteus M, Yu H. Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks. EMBO J. 2006;25:3377-88 pubmed
    ..Our results establish a mechanism by which the hSMC5/6 complex promotes DNA repair and suggest a novel strategy to improve the efficiency of gene targeting in mammalian somatic cells. ..
  2. Taylor E, Moghraby J, Lees J, Smit B, Moens P, Lehmann A. Characterization of a novel human SMC heterodimer homologous to the Schizosaccharomyces pombe Rad18/Spr18 complex. Mol Biol Cell. 2001;12:1583-94 pubmed
    ..We have now isolated the human orthologues of rad18 and spr18 and designated them hSMC6 and hSMC5...
  3. Wu N, Kong X, Ji Z, Zeng W, Potts P, Yokomori K, et al. Scc1 sumoylation by Mms21 promotes sister chromatid recombination through counteracting Wapl. Genes Dev. 2012;26:1473-85 pubmed publisher
    ..We propose that Scc1 sumoylation by Mms21 promotes SCR by antagonizing Wapl at a step after cohesin loading at DSBs and in a way not solely dependent on Smc3 acetylation. ..
  4. Aragon L. The Smc5/6 Complex: New and Old Functions of the Enigmatic Long-Distance Relative. Annu Rev Genet. 2018;52:89-107 pubmed publisher
    Smc5 and Smc6, together with the kleisin Nse4, form the heart of the enigmatic and poorly understood Smc5/6 complex, which is frequently viewed as a cousin of cohesin and condensin with functions in DNA repair...
  5. Oravcová M, Boddy M. Recruitment, loading, and activation of the Smc5-Smc6 SUMO ligase. Curr Genet. 2019;: pubmed publisher
    ..In this regard, we recently showed that like Rtt107, Brc1 supports key functions of the Smc5-Smc6 complex, including its recruitment into DNA repair foci, chromatin association, and SUMO ligase activity...
  6. Oravcová M, Gadaleta M, Nie M, Reubens M, Limbo O, Russell P, et al. Brc1 Promotes the Focal Accumulation and SUMO Ligase Activity of Smc5-Smc6 during Replication Stress. Mol Cell Biol. 2019;39: pubmed publisher
    ..Brc1 is a dosage suppressor of a mutation in the essential Smc5-Smc6 genome stability complex and is thought to act in a bypass pathway...
  7. Choi K, Szakal B, Chen Y, Branzei D, Zhao X. The Smc5/6 complex and Esc2 influence multiple replication-associated recombination processes in Saccharomyces cerevisiae. Mol Biol Cell. 2010;21:2306-14 pubmed publisher
    ..and shu1Delta suppress the sensitivity to the replication-blocking agent methylmethane sulfonate (MMS) in smc6 mutants, with double deletions conferring stronger suppression...
  8. Abdul F, Filleton F, Gerossier L, Paturel A, Hall J, Strubin M, et al. Smc5/6 Antagonism by HBx Is an Evolutionarily Conserved Function of Hepatitis B Virus Infection in Mammals. J Virol. 2018;92: pubmed publisher
    ..Yet, Smc6 showed marks of adaptive evolution, potentially reminiscent of a virus-host "arms race...
  9. Bentley P, Tan M, McBride A, White E, Howley P. The SMC5/6 Complex Interacts with the Papillomavirus E2 Protein and Influences Maintenance of Viral Episomal DNA. J Virol. 2018;92: pubmed publisher
    ..studies and have identified and validated the cellular proteins structural maintenance of chromosome 5 (SMC5) and SMC6 as interactors of the viral E2 protein. These two proteins make up the core components of the SMC5/6 complex...

More Information


  1. Verver D, Langedijk N, Jordan P, Repping S, Hamer G. The SMC5/6 complex is involved in crucial processes during human spermatogenesis. Biol Reprod. 2014;91:22 pubmed publisher
    ..We therefore investigated the role of this complex in human spermatogenesis. We found SMC6 to be expressed in the human testis and present in a subset of type Adark and type Apale spermatogonia, all ..
  2. Sánchez A, Roguev A, Krogan N, Russell P. Genetic Interaction Landscape Reveals Critical Requirements for Schizosaccharomyces pombe Brc1 in DNA Damage Response Mutants. G3 (Bethesda). 2015;5:953-62 pubmed publisher
    Brc1, which was first identified as a high-copy, allele-specific suppressor of a mutation impairing the Smc5-Smc6 holocomplex in Schizosaccharomyces pombe, protects genome integrity during normal DNA replication and when cells are exposed ..
  3. Xue X, Choi K, Bonner J, Chiba T, Kwon Y, Xu Y, et al. Restriction of replication fork regression activities by a conserved SMC complex. Mol Cell. 2014;56:436-45 pubmed publisher
    ..We show that the structural maintenance of chromosome complex Smc5-Smc6 restrains the replication fork regression activity of Mph1 helicase, but not its D loop disruptive activity...
  4. Wang D, Wang L, Zhang Y, Zhao Y, Chen G. Hydrogen gas inhibits lung cancer progression through targeting SMC3. Biomed Pharmacother. 2018;104:788-797 pubmed publisher
    ..Besides, H2 down-regulated the expression of NIBPL, SMC3, SMC5 and SMC6, and also reduced the expression of Cyclin D1, CDK4 and CDK6...
  5. Scherthan H, Schöfisch K, Dell T, Illner D. Contrasting behavior of heterochromatic and euchromatic chromosome portions and pericentric genome separation in pre-bouquet spermatocytes of hybrid mice. Chromosoma. 2014;123:609-24 pubmed publisher
    ..with particular enrichment of epigenetic marks (H3K9me3), HP1-γ and structural maintenance of chromosomes SMC6 complex proteins at the MMU major satellite DNA repeats...
  6. Tran M, Tsarouhas V, Kegel A. Early development of Drosophila embryos requires Smc5/6 function during oogenesis. Biol Open. 2016;5:928-41 pubmed publisher
    ..To investigate Smc5/6 function during early embryogenesis we examined smc5 and smc6 mutants of the fruit fly Drosophila melanogaster using a combination of reverse genetics and microscopy approaches...
  7. Mahendrawada L, Rai R, Kothiwal D, Laloraya S. Interplay between Top1 and Mms21/Nse2 mediated sumoylation in stable maintenance of long chromosomes. Curr Genet. 2017;63:627-645 pubmed publisher
    ..In contrast, an smc6-56 top1 mutant defective in Smc6, another subunit of the Smc5/6 complex, of which Mms21 is a component, did not ..
  8. Liu C, Finke A, Díaz M, Rozhon W, Poppenberger B, Baubec T, et al. Repair of DNA Damage Induced by the Cytidine Analog Zebularine Requires ATR and ATM in Arabidopsis. Plant Cell. 2015;27:1788-800 pubmed publisher
    ..The repair requires a functional STRUCTURAL MAINTENANCE OF CHROMOSOMES5 (SMC5)-SMC6 complex and is accomplished predominantly by synthesis-dependent strand-annealing homologous recombination...
  9. Taniura H, Tanabe N, Bando Y, Arai N. Nse1 and Nse4, subunits of the Smc5-Smc6 complex, are involved in Dictyostelium development upon starvation. Dev Growth Differ. 2015;57:430-43 pubmed publisher
    The Smc5-Smc6 complex contains a heterodimeric core of two SMC proteins and non-Smc elements (Nse1-6), and plays an important role in DNA repair. We investigated the functional roles of Nse4 and Nse1 in Dictyostelium discoideum...
  10. Peng J, Feng W. Incision of damaged DNA in the presence of an impaired Smc5/6 complex imperils genome stability. Nucleic Acids Res. 2016;44:10216-10229 pubmed
    ..Here, we analysed genome-wide replication dynamics in a hypomorphic budding yeast mutant, smc6-P4 The overall replication dynamics in the smc6 mutant is similar to that in the wild-type cells...
  11. Rai R, Laloraya S. Genetic evidence for functional interaction of Smc5/6 complex and Top1 with spatial frequency of replication origins required for maintenance of chromosome stability. Curr Genet. 2017;63:765-776 pubmed publisher
    ..evidence for functional interaction between replication origin distribution and two subunits of the Smc5/6 complex, Smc6 and Mms21, as well as Top1...
  12. Kanno T, Berta D, Sjögren C. The Smc5/6 Complex Is an ATP-Dependent Intermolecular DNA Linker. Cell Rep. 2015;12:1471-82 pubmed publisher
    ..We also show that a complex containing an Smc6 mutant that is defective in ATP binding fails to interact with DNA and chromosomes and leads to cell death with ..
  13. Alshareeda A, Negm O, Green A, Nolan C, Tighe P, Albarakati N, et al. KPNA2 is a nuclear export protein that contributes to aberrant localisation of key proteins and poor prognosis of breast cancer. Br J Cancer. 2015;112:1929-37 pubmed publisher
    ..with the subcellular localisation of key DDR proteins that showed cytoplasmic expression including BRCA1, RAD51, SMC6L1, γH2AX, BARD1, UBC9, PIAS1 and CHK1...
  14. Stephan A, Kliszczak M, Morrison C. The Nse2/Mms21 SUMO ligase of the Smc5/6 complex in the maintenance of genome stability. FEBS Lett. 2011;585:2907-13 pubmed publisher
    ..Recent findings have indicated that Smc5/6 may play a topological role in chromosome dynamics, which may help understand the complexity of its activities. ..
  15. Gallego Paez L, Tanaka H, Bando M, Takahashi M, Nozaki N, Nakato R, et al. Smc5/6-mediated regulation of replication progression contributes to chromosome assembly during mitosis in human cells. Mol Biol Cell. 2014;25:302-17 pubmed publisher
    ..Depletion of Smc5 and Smc6 resulted in aberrant mitotic chromosome phenotypes that were accompanied by the abnormal distribution of ..
  16. Niu C, Livingston C, Li L, Beran R, Daffis S, Ramakrishnan D, et al. 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. 2017;12:e0169648 pubmed publisher
    ..has functional implications since depletion of ND10 structural components alters the nuclear distribution of Smc6 and induces HBV gene expression in the absence of HBx...
  17. Pebernard S, Perry J, Tainer J, Boddy M. Nse1 RING-like domain supports functions of the Smc5-Smc6 holocomplex in genome stability. Mol Biol Cell. 2008;19:4099-109 pubmed publisher
    The Smc5-Smc6 holocomplex plays essential but largely enigmatic roles in chromosome segregation, and facilitates DNA repair. The Smc5-Smc6 complex contains six conserved non-SMC subunits...
  18. Mychaleckyj J, Havt A, Nayak U, Pinkerton R, Farber E, Concannon P, et al. Genome-Wide Analysis in Brazilians Reveals Highly Differentiated Native American Genome Regions. Mol Biol Evol. 2017;34:559-574 pubmed publisher
    ..We found SNPs within or proximal to the genes CIITA (rs6498115), SMC6 (rs1834619), and KLHL29 (rs2288697) were most differentiated in the Amerindian-specific branch, while SNPs in the ..
  19. Cobbe N, Heck M. The evolution of SMC proteins: phylogenetic analysis and structural implications. Mol Biol Evol. 2004;21:332-47 pubmed
    ..In addition, we show that the SMC5 and SMC6 subfamily members have evolved comparatively rapidly and suggest that these proteins may perform redundant ..
  20. Harvey S, Sheedy D, Cuddihy A, O Connell M. Coordination of DNA damage responses via the Smc5/Smc6 complex. Mol Cell Biol. 2004;24:662-74 pubmed
    ..Here we show that the Smc5/Smc6 (Smc5/6) complex is required for a coordinated response to DNA damage and normal chromosome integrity...
  21. Sergeant J, Taylor E, Palecek J, Fousteri M, Andrews E, Sweeney S, et al. Composition and architecture of the Schizosaccharomyces pombe Rad18 (Smc5-6) complex. Mol Cell Biol. 2005;25:172-84 pubmed
    ..Rad18 (Smc6) is a member of the structural maintenance of chromosomes (SMC) family and, together with its SMC partner Spr18 (..
  22. Taylor E, Copsey A, Hudson J, Vidot S, Lehmann A. Identification of the proteins, including MAGEG1, that make up the human SMC5-6 protein complex. Mol Cell Biol. 2008;28:1197-206 pubmed
    ..Depletion also confers sensitivity to methyl methanesulfonate. Several of the components are modified by sumoylation and ubiquitination. ..
  23. Verver D, Zheng Y, Speijer D, Hoebe R, Dekker H, Repping S, et al. Non-SMC Element 2 (NSMCE2) of the SMC5/6 Complex Helps to Resolve Topological Stress. Int J Mol Sci. 2016;17: pubmed
    ..We therefore propose that the SMC5/6 complex functions in resolving TOP2A-mediated DSB-repair intermediates generated during replication. ..
  24. Jeppsson K, Kanno T, Shirahige K, Sjögren C. The maintenance of chromosome structure: positioning and functioning of SMC complexes. Nat Rev Mol Cell Biol. 2014;15:601-14 pubmed publisher
  25. Decorsière A, Mueller H, van Breugel P, Abdul F, Gerossier L, Beran R, et al. Hepatitis B virus X protein identifies the Smc5/6 complex as a host restriction factor. Nature. 2016;531:386-9 pubmed publisher
    ..By destroying this complex, HBx relieves the inhibition to allow productive hepatitis B virus gene expression. ..
  26. Räschle M, Smeenk G, Hansen R, Temu T, Oka Y, Hein M, et al. DNA repair. Proteomics reveals dynamic assembly of repair complexes during bypass of DNA cross-links. Science. 2015;348:1253671 pubmed publisher
    ..Our study provides a global analysis of an entire DNA repair pathway and reveals the mechanism of SMC5/6 relocalization to damaged DNA in vertebrate cells. ..
  27. Reubens M, Rozenzhak S, Russell P. Multi-BRCT Domain Protein Brc1 Links Rhp18/Rad18 and ?H2A To Maintain Genome Stability during S Phase. Mol Cell Biol. 2017;37: pubmed publisher
    ..Brc1 binding to Rhp18 and ?H2A are required for the Brc1 overexpression suppression of smc6-74, a mutation that impairs the Smc5/6 structural maintenance of chromosomes complex required for chromosome ..
  28. Potts P, Yu H. The SMC5/6 complex maintains telomere length in ALT cancer cells through SUMOylation of telomere-binding proteins. Nat Struct Mol Biol. 2007;14:581-90 pubmed
    ..Thus, the SMC5/6 complex facilitates telomere HR and elongation in ALT cells by promoting APB formation through SUMOylation of telomere-binding proteins. ..
  29. Potts P, Yu H. Human MMS21/NSE2 is a SUMO ligase required for DNA repair. Mol Cell Biol. 2005;25:7021-32 pubmed
    ..Here we show that the human homolog of MMS21 is also a SUMO ligase. hMMS21 stimulates sumoylation of hSMC6 and the DNA repair protein TRAX...
  30. Murphy C, Xu Y, Li F, Nio K, Reszka Blanco N, Li X, et al. Hepatitis B Virus X Protein Promotes Degradation of SMC5/6 to Enhance HBV Replication. Cell Rep. 2016;16:2846-2854 pubmed publisher
    ..proteomics, we identified the structural maintenance of chromosomes (SMC) complex proteins SMC5 and SMC6 as CRL4(HBx) substrates...