Gene Symbol: SMC6
Description: DNA repair protein SMC6
Alias: RHC18, DNA repair protein SMC6
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Lilienthal I, Kanno T, Sjögren C. Inhibition of the Smc5/6 complex during meiosis perturbs joint molecule formation and resolution without significantly changing crossover or non-crossover levels. PLoS Genet. 2013;9:e1003898 pubmed publisher
    ..Establishment and removal of meiotic sister chromatid cohesin are independent of functional Smc6 protein. smc6 mutants also have normal levels of DSB formation and repair...
  2. Zhao X, Blobel G. A SUMO ligase is part of a nuclear multiprotein complex that affects DNA repair and chromosomal organization. Proc Natl Acad Sci U S A. 2005;102:4777-82 pubmed
    ..of small ubiquitin-like modifier (SUMO) ligases, two structural-maintenance-of-chromosome (Smc) proteins, Smc5 and Smc6, and a protein that contains an ubiquitin ligase signature domain...
  3. Yong Gonzales V, Hang L, Castellucci F, Branzei D, Zhao X. The Smc5-Smc6 complex regulates recombination at centromeric regions and affects kinetochore protein sumoylation during normal growth. PLoS ONE. 2012;7:e51540 pubmed publisher
    The Smc5-Smc6 complex in Saccharomyces cerevisiae is both essential for growth and important for coping with genotoxic stress...
  4. Noël J, Wellinger R. Abrupt telomere losses and reduced end-resection can explain accelerated senescence of Smc5/6 mutants lacking telomerase. DNA Repair (Amst). 2011;10:271-82 pubmed publisher
  5. Chavez A, Agrawal V, Johnson F. Homologous recombination-dependent rescue of deficiency in the structural maintenance of chromosomes (Smc) 5/6 complex. J Biol Chem. 2011;286:5119-25 pubmed publisher
    The essential and evolutionarily conserved Smc5-Smc6 complex (Smc5/6) is critical for the maintenance of genome stability...
  6. Lindroos H, Ström L, Itoh T, Katou Y, Shirahige K, Sjögren C. Chromosomal association of the Smc5/6 complex reveals that it functions in differently regulated pathways. Mol Cell. 2006;22:755-67 pubmed
    ..Additionally, localization of Smc6 to collapsed replication forks indicates an involvement in their rescue...
  7. Torres Rosell J, Sunjevaric I, De Piccoli G, Sacher M, Eckert Boulet N, Reid R, et al. The Smc5-Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus. Nat Cell Biol. 2007;9:923-31 pubmed
    ..The nucleolar exclusion of Rad52 recombination foci entails Mre11 and Smc5-Smc6 complexes and depends on Rad52 SUMO (small ubiquitin-related modifier) modification...
  8. Chen Y, Choi K, Szakal B, Arenz J, Duan X, Ye H, et al. Interplay between the Smc5/6 complex and the Mph1 helicase in recombinational repair. Proc Natl Acad Sci U S A. 2009;106:21252-7 pubmed publisher
    ..We suggest that the Smc5/6 complex can counteract/modulate a pro-recombinogenic function of Mph1 or facilitate the resolution of recombination structures generated by Mph1. ..
  9. 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...

More Information


  1. Chavez A, George V, Agrawal V, Johnson F. Sumoylation and the structural maintenance of chromosomes (Smc) 5/6 complex slow senescence through recombination intermediate resolution. J Biol Chem. 2010;285:11922-30 pubmed publisher
    ..One target of Mms21-dependent sumoylation is the cohesin- and condensin-related Smc5-Smc6 complex (Smc5/6)...
  2. Hwang J, Smith S, Ceschia A, Torres Rosell J, Aragon L, Myung K. Smc5-Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications. DNA Repair (Amst). 2008;7:1426-36 pubmed publisher
    ..The smc6-9 mutation increased the translocation class gross chromosomal rearrangement (GCR)...
  3. Takahashi Y, Dulev S, Liu X, Hiller N, Zhao X, Strunnikov A. Cooperation of sumoylated chromosomal proteins in rDNA maintenance. PLoS Genet. 2008;4:e1000215 pubmed publisher
    ..In addition, binding of cohesin and condensin to rDNA is altered in the mms21-CH E3-deficient mutant. ..
  4. Duan X, Yang Y, Chen Y, Arenz J, Rangi G, Zhao X, et al. 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. J Biol Chem. 2009;284:8507-15 pubmed publisher
    ..We have previously shown that the Smc5/6 complex of Saccharomyces cerevisiae contains Smc5, Smc6, and six non-SMC elements (Nse1-6)...
  5. Duan X, Sarangi P, Liu X, Rangi G, Zhao X, Ye H. Structural and functional insights into the roles of the Mms21 subunit of the Smc5/6 complex. Mol Cell. 2009;35:657-68 pubmed publisher
    ..Through structure-based dissection of Mms21 functions, our studies establish a framework for understanding its roles in the Smc5/6 complex. ..
  6. Sollier J, Driscoll R, Castellucci F, Foiani M, Jackson S, Branzei D. The Saccharomyces cerevisiae Esc2 and Smc5-6 proteins promote sister chromatid junction-mediated intra-S repair. Mol Biol Cell. 2009;20:1671-82 pubmed publisher
  7. De Piccoli G, Cortes Ledesma F, Ira G, Torres Rosell J, Uhle S, Farmer S, et al. Smc5-Smc6 mediate DNA double-strand-break repair by promoting sister-chromatid recombination. Nat Cell Biol. 2006;8:1032-4 pubmed
    ..Here, we show that the Smc5-Smc6 complex is recruited to DSBs de novo to support their repair by homologous recombination between sister chromatids...
  8. Cost G, Cozzarelli N. Smc5p promotes faithful chromosome transmission and DNA repair in Saccharomyces cerevisiae. Genetics. 2006;172:2185-200 pubmed
    ..Our data indicate a critical role for the S. cerevisiae Smc5/6-containing complexes in both DNA repair and chromosome segregation. ..
  9. Onoda F, Takeda M, Seki M, Maeda D, Tajima J, Ui A, et al. SMC6 is required for MMS-induced interchromosomal and sister chromatid recombinations in Saccharomyces cerevisiae. DNA Repair (Amst). 2004;3:429-39 pubmed
    SMC6 (RHC18) in Saccharomyces cerevisiae, which is a homologue of the Schizosaccharomyces pombe rad18+ gene and essential for cell viability, encodes a structural maintenance of chromosomes (SMC) family protein...
  10. Torres Rosell J, Machin F, Farmer S, Jarmuz A, Eydmann T, Dalgaard J, et al. SMC5 and SMC6 genes are required for the segregation of repetitive chromosome regions. Nat Cell Biol. 2005;7:412-9 pubmed
    Structure chromosome (SMC) proteins organize the core of cohesin, condensin and Smc5-Smc6 complexes. The Smc5-Smc6 complex is required for DNA repair, as well as having another essential but enigmatic function...
  11. Xue X, Choi K, Bonner J, Szakal B, Chen Y, Papusha A, et al. Selective modulation of the functions of a conserved DNA motor by a histone fold complex. Genes Dev. 2015;29:1000-5 pubmed publisher
    ..Thus, scMHF is a function-specific enhancer of Mph1 that enables flexible response to different genome repair situations. ..
  12. Silva S, Altmannova V, Luke Glaser S, Henriksen P, Gallina I, Yang X, et al. Mte1 interacts with Mph1 and promotes crossover recombination and telomere maintenance. Genes Dev. 2016;30:700-17 pubmed publisher
    ..Taken together, our data indicate that Mte1 plays a role in regulation of crossover recombination, response to replication stress, and telomere maintenance. ..
  13. Bermúdez López M, Pociño Merino I, Sánchez H, Bueno A, Guasch C, Almedawar S, et al. ATPase-dependent control of the Mms21 SUMO ligase during DNA repair. PLoS Biol. 2015;13:e1002089 pubmed publisher
  14. Laflamme G, Tremblay Boudreault T, Roy M, Andersen P, Bonneil E, Atchia K, et al. Structural maintenance of chromosome (SMC) proteins link microtubule stability to genome integrity. J Biol Chem. 2014;289:27418-31 pubmed publisher
    ..Collectively, these findings demonstrate that SMC proteins can bind to and stabilize microtubules and that SMC-microtubule interactions are essential to establish a robust system to maintain genome integrity. ..
  15. Ohouo P, Smolka M. A touching moment for Smc5/6: from ssDNA binding to repair. Cell Cycle. 2011;10:1190-1 pubmed
  16. Xue X, Papusha A, Choi K, Bonner J, Kumar S, Niu H, et al. Differential regulation of the anti-crossover and replication fork regression activities of Mph1 by Mte1. Genes Dev. 2016;30:687-99 pubmed publisher
    ..We further show that the influence of Mte1 on Mph1 activities requires its binding to Mph1 and DNA. Thus, Mte1 differentially regulates Mph1 activities to achieve distinct outcomes in recombination and replication fork repair. ..
  17. Moradi Fard S, Sarthi J, Tittel Elmer M, Lalonde M, Cusanelli E, Chartrand P, et al. Smc5/6 Is a Telomere-Associated Complex that Regulates Sir4 Binding and TPE. PLoS Genet. 2016;12:e1006268 pubmed publisher
    ..These findings support a role for Smc5/6 in telomere maintenance that is separate from its canonical role(s) in HR-mediated events during replication and telomere elongation. ..
  18. Jeppsson K, Carlborg K, Nakato R, Berta D, Lilienthal I, Kanno T, et al. The chromosomal association of the Smc5/6 complex depends on cohesion and predicts the level of sister chromatid entanglement. PLoS Genet. 2014;10:e1004680 pubmed publisher
    ..These are most likely SCIs, and our results thus indicate that, at least when Top2 is inhibited, Smc5/6 facilitates their resolution. ..
  19. Tapia Alveal C, Lin S, O Connell M. Functional interplay between cohesin and Smc5/6 complexes. Chromosoma. 2014;123:437-45 pubmed publisher
    ..However, they also release their embrace of sister chromatids to enable their segregation at anaphase, resetting the dynamic cycle of SMC-chromosome interactions. ..
  20. Leung G, Lee L, Schmidt T, Shirahige K, Kobor M. Rtt107 is required for recruitment of the SMC5/6 complex to DNA double strand breaks. J Biol Chem. 2011;286:26250-7 pubmed publisher
    ..Genetic analyses revealed that, although a subset of Rtt107 and SMC5/6 functions was shared, these proteins also contributed independently to maintenance of genome integrity. ..
  21. Santa Maria S, Gangavarapu V, Johnson R, Prakash L, Prakash S. Requirement of Nse1, a subunit of the Smc5-Smc6 complex, for Rad52-dependent postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae. Mol Cell Biol. 2007;27:8409-18 pubmed
    ..In this study, we present evidence for the requirement of Nse1, a subunit of the Smc5-Smc6 complex, in Rad52-dependent PRR, and our genetic analyses suggest a role for the Nse1 and Mms21 E3 ligase ..
  22. Daee D, Ferrari E, Longerich S, Zheng X, Xue X, Branzei D, et al. Rad5-dependent DNA repair functions of the Saccharomyces cerevisiae FANCM protein homolog Mph1. J Biol Chem. 2012;287:26563-75 pubmed publisher
    ..These studies reveal the functional conservation of the FA pathway and validate the yeast model for future studies to further elucidate the mechanism of the FA pathway. ..
  23. Choi K, Batke S, Szakal B, Lowther J, Hao F, Sarangi P, et al. Concerted and differential actions of two enzymatic domains underlie Rad5 contributions to DNA damage tolerance. Nucleic Acids Res. 2015;43:2666-77 pubmed publisher
    ..These findings delineate how two Rad5 enzymatic domains concertedly influence PCNA modification, and unveil their discrete contributions to stress tolerance. ..
  24. 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 ..
  25. Menolfi D, Delamarre A, Lengronne A, Pasero P, Branzei D. Essential Roles of the Smc5/6 Complex in Replication through Natural Pausing Sites and Endogenous DNA Damage Tolerance. Mol Cell. 2015;60:835-46 pubmed publisher
  26. 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 ..
  27. 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...
  28. 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...
  29. Ohouo P, Bastos de Oliveira F, Almeida B, Smolka M. DNA damage signaling recruits the Rtt107-Slx4 scaffolds via Dpb11 to mediate replication stress response. Mol Cell. 2010;39:300-6 pubmed publisher
    ..Our results unveil how Mec1 regulates the Slx4 and Rtt107 scaffolds and establish a mechanistic link between DNA damage signaling and fork repair. ..
  30. Horigome C, Bustard D, Marcomini I, Delgoshaie N, Tsai Pflugfelder M, Cobb J, et al. PolySUMOylation by Siz2 and Mms21 triggers relocation of DNA breaks to nuclear pores through the Slx5/Slx8 STUbL. Genes Dev. 2016;30:931-45 pubmed publisher
    ..Slx5/Slx8 and binding to pores favor repair by ectopic break-induced replication and imprecise end-joining. ..
  31. Lafuente Barquero J, Luke Glaser S, Graf M, Silva S, Gómez González B, Lockhart A, et al. The Smc5/6 complex regulates the yeast Mph1 helicase at RNA-DNA hybrid-mediated DNA damage. PLoS Genet. 2017;13:e1007136 pubmed publisher
    ..The data presented here support a model, where Mph1's helicase activity plays a crucial role in responding to persistent RNA-DNA hybrids. ..
  32. Chen Y, Szakal B, Castellucci F, Branzei D, Zhao X. DNA damage checkpoint and recombinational repair differentially affect the replication stress tolerance of Smc6 mutants. Mol Biol Cell. 2013;24:2431-41 pubmed publisher
    ..mph1 is known to reduce the levels of recombination intermediates in smc6 mutants. Here, we show that mph1 also hyperactivates the Mec1 checkpoint...
  33. Fujioka Y, Kimata Y, Nomaguchi K, Watanabe K, Kohno K. Identification of a novel non-structural maintenance of chromosomes (SMC) component of the SMC5-SMC6 complex involved in DNA repair. J Biol Chem. 2002;277:21585-91 pubmed
    ..They have been classified into six subtypes, termed SMC1 to SMC6, and function as heterodimer components of large protein complexes that also include several non-SMC proteins...
  34. Torres Rosell J, Machin F, Aragon L. Smc5-Smc6 complex preserves nucleolar integrity in S. cerevisiae. Cell Cycle. 2005;4:868-72 pubmed
    ..A third complex containing Smc proteins at its core, the Smc5-Smc6 complex, previously known to be involved in DNA repair has recently been shown to contribute to chromosome ..
  35. Watanabe Y. The importance of being Smc5/6. Nat Cell Biol. 2005;7:329-31 pubmed