Gene Symbol: SMC3
Description: cohesin subunit SMC3
Alias: cohesin subunit SMC3
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Michaelis C, Ciosk R, Nasmyth K. Cohesins: chromosomal proteins that prevent premature separation of sister chromatids. Cell. 1997;91:35-45 pubmed
    ..Proteins homologous to Scc1p exist in a variety of eukaryotic organisms including humans. A common cohesion apparatus might be used by all eukaryotic cells during both mitosis and meiosis. ..
  2. Toth A, Ciosk R, Uhlmann F, Galova M, Schleiffer A, Nasmyth K. Yeast cohesin complex requires a conserved protein, Eco1p(Ctf7), to establish cohesion between sister chromatids during DNA replication. Genes Dev. 1999;13:320-33 pubmed
    ..The sixth protein, Eco1p(Ctf7p), is not a Cohesin subunit. It is necessary for the establishment of cohesion during DNA replication but not for its maintenance during G2 and M phases. ..
  3. Sutani T, Kawaguchi T, Kanno R, Itoh T, Shirahige K. Budding yeast Wpl1(Rad61)-Pds5 complex counteracts sister chromatid cohesion-establishing reaction. Curr Biol. 2009;19:492-7 pubmed publisher
    ..cohesin with G2 phase chromosomes and that Eco1 promotes dissociation of Wpl1-Pds5 from cohesin via acetylation of Smc3, a cohesin subunit...
  4. Mishra A, Hu B, Kurze A, Beckouët F, Farcas A, Dixon S, et al. Both interaction surfaces within cohesin's hinge domain are essential for its stable chromosomal association. Curr Biol. 2010;20:279-89 pubmed publisher
    The cohesin complex that mediates sister chromatid cohesion contains three core subunits: Smc1, Smc3, and Scc1...
  5. Chan K, Roig M, Hu B, Beckouët F, Metson J, Nasmyth K. Cohesin's DNA exit gate is distinct from its entrance gate and is regulated by acetylation. Cell. 2012;150:961-74 pubmed publisher
    Sister chromatid cohesion is mediated by entrapment of sister DNAs by a tripartite ring composed of cohesin's Smc1, Smc3, and α-kleisin subunits...
  6. Lengronne A, Katou Y, Mori S, Yokobayashi S, Kelly G, Itoh T, et al. Cohesin relocation from sites of chromosomal loading to places of convergent transcription. Nature. 2004;430:573-8 pubmed
    ..Cohesin localization to places of convergent transcription is conserved in fission yeast, suggesting that it is a common feature of eukaryotic chromosomes. ..
  7. Heidinger Pauli J, Unal E, Koshland D. Distinct targets of the Eco1 acetyltransferase modulate cohesion in S phase and in response to DNA damage. Mol Cell. 2009;34:311-21 pubmed publisher
    ..We show that Mcd1p and Smc3p acetylation antagonize Wpl1p only in their proper context. Thus, Eco1p antagonizes Wpl1p in distinct ways to modulate cohesion generation during the cell cycle and after DNA damage. ..
  8. Rolef Ben Shahar T, Heeger S, Lehane C, East P, Flynn H, Skehel M, et al. Eco1-dependent cohesin acetylation during establishment of sister chromatid cohesion. Science. 2008;321:563-6 pubmed publisher
    ..An acetylation-mimicking mutation of a conserved lysine in cohesin's Smc3 subunit makes Eco1 dispensable for cell growth, and we show that Smc3 is acetylated in an Eco1-dependent manner ..
  9. Zhang J, Shi X, Li Y, Kim B, Jia J, Huang Z, et al. Acetylation of Smc3 by Eco1 is required for S phase sister chromatid cohesion in both human and yeast. Mol Cell. 2008;31:143-51 pubmed publisher
    ..Here we report that yeast Eco1 and its human ortholog, ESCO1, both acetylate Smc3, a component of the cohesin complex that physically holds the sister chromatid together, at two conserved lysine ..

More Information


  1. Weitzer S, Lehane C, Uhlmann F. A model for ATP hydrolysis-dependent binding of cohesin to DNA. Curr Biol. 2003;13:1930-40 pubmed
    ..After DNA replication, two DNA strands may be trapped to promote sister chromatid cohesion. In anaphase, Scc1 cleavage opens the ring to release sister chromatids. ..
  2. Farcas A, Uluocak P, Helmhart W, Nasmyth K. Cohesin's concatenation of sister DNAs maintains their intertwining. Mol Cell. 2011;44:97-107 pubmed publisher
    ..We conclude that by retarding Topo II-driven decatenation, cohesin mediates sister chromatid cohesion by an indirect mechanism as well as one involving entrapment of sister DNAs inside its tripartite ring. ..
  3. Rowland B, Roig M, Nishino T, Kurze A, Uluocak P, Mishra A, et al. Building sister chromatid cohesion: smc3 acetylation counteracts an antiestablishment activity. Mol Cell. 2009;33:763-74 pubmed publisher
    Cohesin's Smc1, Smc3, and Scc1 subunits form a tripartite ring that entraps sister DNAs. Scc3, Pds5, and Rad61 (Wapl) are regulatory subunits that control this process...
  4. Klein F, Mahr P, Galova M, Buonomo S, Michaelis C, Nairz K, et al. A central role for cohesins in sister chromatid cohesion, formation of axial elements, and recombination during yeast meiosis. Cell. 1999;98:91-103 pubmed
    ..The eukaryotic cell's cohesion apparatus is required both for the repair of recombinogenic lesions and for chromosome segregation and therefore appears to lie at the heart of the meiotic process. ..
  5. Borges V, Lehane C, Lopez Serra L, Flynn H, Skehel M, Rolef Ben Shahar T, et al. Hos1 deacetylates Smc3 to close the cohesin acetylation cycle. Mol Cell. 2010;39:677-88 pubmed publisher
    ..During S phase, the replication fork-associated acetyltransferase Eco1 acetylates the cohesin subunit Smc3 to promote the establishment of sister chromatid cohesion...
  6. Petronczki M, Matos J, Mori S, Gregan J, Bogdanova A, Schwickart M, et al. Monopolar attachment of sister kinetochores at meiosis I requires casein kinase 1. Cell. 2006;126:1049-64 pubmed
  7. Arumugam P, Nishino T, Haering C, Gruber S, Nasmyth K. Cohesin's ATPase activity is stimulated by the C-terminal Winged-Helix domain of its kleisin subunit. Curr Biol. 2006;16:1998-2008 pubmed
    ..Cohesin consists of four core subunits, namely Smc1, Smc3, Scc1, and Scc3...
  8. Mc Intyre J, Muller E, Weitzer S, Snydsman B, Davis T, Uhlmann F. In vivo analysis of cohesin architecture using FRET in the budding yeast Saccharomyces cerevisiae. EMBO J. 2007;26:3783-93 pubmed
    ..The circumference consists of the Smc1 and Smc3 subunits, while Scc1 is thought to close the ring by bridging the Smc (structural maintenance of chromosomes) ..
  9. Arumugam P, Gruber S, Tanaka K, Haering C, Mechtler K, Nasmyth K. ATP hydrolysis is required for cohesin's association with chromosomes. Curr Biol. 2003;13:1941-53 pubmed
    ..Cohesin contains four core subunits: Smc1, Smc3, Scc1, and Scc3...
  10. Mayer M, Gygi S, Aebersold R, Hieter P. Identification of RFC(Ctf18p, Ctf8p, Dcc1p): an alternative RFC complex required for sister chromatid cohesion in S. cerevisiae. Mol Cell. 2001;7:959-70 pubmed
  11. Unal E, Heidinger Pauli J, Kim W, Guacci V, Onn I, Gygi S, et al. A molecular determinant for the establishment of sister chromatid cohesion. Science. 2008;321:566-9 pubmed publisher
    ..b>Smc3 head acetylation and its cell cycle regulation provide important insights into the biology and mechanism of ..
  12. Beckouët F, Hu B, Roig M, Sutani T, Komata M, Uluocak P, et al. An Smc3 acetylation cycle is essential for establishment of sister chromatid cohesion. Mol Cell. 2010;39:689-99 pubmed publisher thought to involve entrapment of sister DNAs by a tripartite ring composed of the cohesin subunits Smc1, Smc3, and Scc1...
  13. Haering C, L we J, Hochwagen A, Nasmyth K. Molecular architecture of SMC proteins and the yeast cohesin complex. Mol Cell. 2002;9:773-88 pubmed
    Sister chromatids are held together by the multisubunit cohesin complex, which contains two SMC (Smc1 and Smc3) and two non-SMC (Scc1 and Scc3) proteins...
  14. Gruber S, Haering C, Nasmyth K. Chromosomal cohesin forms a ring. Cell. 2003;112:765-77 pubmed
    The cohesin complex is essential for sister chromatid cohesion during mitosis. Its Smc1 and Smc3 subunits are rod-shaped molecules with globular ABC-like ATPases at one end and dimerization domains at the other connected by long coiled ..
  15. Heidinger Pauli J, Onn I, Koshland D. Genetic evidence that the acetylation of the Smc3p subunit of cohesin modulates its ATP-bound state to promote cohesion establishment in Saccharomyces cerevisiae. Genetics. 2010;185:1249-56 pubmed publisher
    ..Finally, we provide evidence that Smc3p acetylation, which has an essential role in cohesion establishment, modulates the Smc3p ATP-bound state. ..
  16. Xiong B, Lu S, Gerton J. Hos1 is a lysine deacetylase for the Smc3 subunit of cohesin. Curr Biol. 2010;20:1660-5 pubmed publisher
    ..cohesion is established during S phase, and this process requires the four subunits of the cohesin complex (Smc1, Smc3, Mcd1/Scc1, and Irr1/Scc3) and the acetyltransferase Eco1 [10-13]...
  17. Kulemzina I, Schumacher M, Verma V, Reiter J, Metzler J, Failla A, et al. Cohesin rings devoid of Scc3 and Pds5 maintain their stable association with the DNA. PLoS Genet. 2012;8:e1002856 pubmed publisher
    ..The ring is composed of three proteins: Smc1, Smc3 and Scc1...
  18. 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. ..
  19. Lai M, Seki M, Tada S, Enomoto T. Rmi1 functions in S phase-mediated cohesion establishment via a pathway involving the Ctf18-RFC complex and Mrc1. Biochem Biophys Res Commun. 2012;427:682-6 pubmed publisher
    ..both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3. On the other hand, Rmi1 seemed to function in a pathway involving the Ctf18-RFC complex and Mrc1, which were ..
  20. Sundin B, Chiu C, Riffle M, Davis T, Muller E. Localization of proteins that are coordinately expressed with Cln2 during the cell cycle. Yeast. 2004;21:793-800 pubmed
    ..A complete list of localizations, along with images, can be found at our website ( ..
  21. Orgil O, Mor H, Matityahu A, Onn I. Identification of a region in the coiled-coil domain of Smc3 that is essential for cohesin activity. Nucleic Acids Res. 2016;44:6309-17 pubmed publisher
    ..Cohesin's core is composed of two structural maintenance of chromosome (SMC) proteins, called Smc1 and Smc3. SMC proteins are built from a globular hinge domain, a rod-shaped domain composed of long anti-parallel coiled-..
  22. Lu S, Goering M, Gard S, Xiong B, McNairn A, Jaspersen S, et al. Eco1 is important for DNA damage repair in S. cerevisiae. Cell Cycle. 2010;9:3315-27 pubmed publisher
    ..Our results suggest that Eco1 promotes the reciprocal exchange of chromosome arms and maintenance of heterozygosity during mitosis. ..
  23. Huang J, Hsu J, Laurent B. The RSC nucleosome-remodeling complex is required for Cohesin's association with chromosome arms. Mol Cell. 2004;13:739-50 pubmed
    ..Our data suggest a role for RSC in facilitating the loading of cohesin specifically onto chromosome arms, thereby ensuring sister chromatid cohesion and proper chromosome segregation. ..
  24. Wu C, Chen Y, Gartenberg M. Targeted sister chromatid cohesion by Sir2. PLoS Genet. 2011;7:e1002000 pubmed publisher
    ..Taken together, these data define a unique role for Sir2 in cohesion of silent chromatin that is distinct from the enzyme's role as a histone deacetylase. ..
  25. Fernius J, Nerusheva O, Galander S, Alves F, Rappsilber J, Marston A. Cohesin-dependent association of scc2/4 with the centromere initiates pericentromeric cohesion establishment. Curr Biol. 2013;23:599-606 pubmed publisher
    ..Overall, our findings provide a paradigm for the spatial and temporal control of cohesin loading. ..
  26. Cortes Ledesma F, Aguilera A. Double-strand breaks arising by replication through a nick are repaired by cohesin-dependent sister-chromatid exchange. EMBO Rep. 2006;7:919-26 pubmed
    ..provide molecular evidence that cohesins are required for repair of replication-born DSBs by SCE, as determined in smc3, scc1 and scc2 mutants, but not for other recombinational repair events...
  27. White E, Cowan C, Cande W, Kaback D. In vivo analysis of synaptonemal complex formation during yeast meiosis. Genetics. 2004;167:51-63 pubmed
    ..ZIP1::GFP also facilitated the enrichment of fluorescent SC and the identification of meiosis-specific proteins by MALDI-TOF mass spectroscopy. ..
  28. Beckouët F, Srinivasan M, Roig M, Chan K, Scheinost J, Batty P, et al. Releasing Activity Disengages Cohesin's Smc3/Scc1 Interface in a Process Blocked by Acetylation. Mol Cell. 2016;61:563-574 pubmed publisher
    ..cohesion conferred by entrapment of sister DNAs within a tripartite ring formed between cohesin's Scc1, Smc1, and Smc3 subunits is created during S and destroyed at anaphase through Scc1 cleavage by separase...
  29. 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. ..
  30. Çamdere G, Guacci V, Stricklin J, Koshland D. The ATPases of cohesin interface with regulators to modulate cohesin-mediated DNA tethering. elife. 2015;4: pubmed publisher
    ..Cohesin contains a heterodimeric ATP-binding Cassette (ABC) ATPase comprised of Smc1 and Smc3 ATPase active sites. These ATPases are required for cohesin to bind DNA...
  31. Pakchuen S, Ishibashi M, Takakusagi E, Shirahige K, Sutani T. Physical Association of Saccharomyces cerevisiae Polo-like Kinase Cdc5 with Chromosomal Cohesin Facilitates DNA Damage Response. J Biol Chem. 2016;291:17228-46 pubmed publisher
  32. Litwin I, Bakowski T, Maciaszczyk Dziubinska E, Wysocki R. The LSH/HELLS homolog Irc5 contributes to cohesin association with chromatin in yeast. Nucleic Acids Res. 2017;45:6404-6416 pubmed publisher
    ..Our results suggest that Irc5 is an auxiliary factor that is involved in cohesin association with chromatin. ..
  33. Hirano T. SMC-mediated chromosome mechanics: a conserved scheme from bacteria to vertebrates?. Genes Dev. 1999;13:11-9 pubmed
  34. Mishra P, Ciftci Yilmaz S, Reynolds D, Au W, Boeckmann L, Dittman L, et al. Polo kinase Cdc5 associates with centromeres to facilitate the removal of centromeric cohesin during mitosis. Mol Biol Cell. 2016;27:2286-300 pubmed publisher
    ..Cohesin removal from centromeric chromatin requires Cdc5 but removal at distal chromosomal arm sites does not. Our results define a novel role for Cdc5 in regulating removal of centromeric cohesins and faithful chromosome segregation. ..
  35. Li S, Yue Z, Tanaka T. Smc3 Deacetylation by Hos1 Facilitates Efficient Dissolution of Sister Chromatid Cohesion during Early Anaphase. Mol Cell. 2017;68:605-614.e4 pubmed publisher
    ..During this process, cohesin Smc3 undergoes a cycle of acetylation: Smc3 acetylation by Eco1 in S phase stabilizes cohesin association with ..
  36. Maradeo M, Garg A, Skibbens R. Rfc5p regulates alternate RFC complex functions in sister chromatid pairing reactions in budding yeast. Cell Cycle. 2010;9:4370-8 pubmed
    ..pathways in that rfc5-1 greatly accentuates growth defects when expressed in scc2 (deposition), mcd1/scc1 or smc3 (cohesion maintenance) mutated cells...
  37. Parnas O, Zipin Roitman A, Mazor Y, Liefshitz B, Ben Aroya S, Kupiec M. The ELG1 clamp loader plays a role in sister chromatid cohesion. PLoS ONE. 2009;4:e5497 pubmed publisher
    ..Our results suggest that Elg1, Ctf4, and Ctf18 may coordinate the relative movement of the replication fork with respect to the cohesin ring. ..
  38. de Jager M, Trujillo K, Sung P, Hopfner K, Carney J, Tainer J, et al. Differential arrangements of conserved building blocks among homologs of the Rad50/Mre11 DNA repair protein complex. J Mol Biol. 2004;339:937-49 pubmed
    ..cerevisiae SMC1/SMC3 cohesin SMC complexes...
  39. Kagansky A, Freeman L, Lukyanov D, Strunnikov A. Histone tail-independent chromatin binding activity of recombinant cohesin holocomplex. J Biol Chem. 2004;279:3382-8 pubmed
    ..Histone tails and ATP are dispensable for cohesin binding to chromatin in this reaction. A model for cohesin association with chromatin is proposed. ..
  40. Li Z, Vizeacoumar F, Bahr S, Li J, Warringer J, Vizeacoumar F, et al. Systematic exploration of essential yeast gene function with temperature-sensitive mutants. Nat Biotechnol. 2011;29:361-7 pubmed publisher
    ..This mutant collection should facilitate a wide range of systematic studies aimed at understanding the functions of essential genes. ..
  41. Kurze A, Michie K, Dixon S, Mishra A, Itoh T, Khalid S, et al. A positively charged channel within the Smc1/Smc3 hinge required for sister chromatid cohesion. EMBO J. 2011;30:364-78 pubmed publisher
    Cohesin's structural maintenance of chromosome 1 (Smc1) and Smc3 are rod-shaped proteins with 50-nm long intra-molecular coiled-coil arms with a heterodimerization domain at one end and an ABC-like nucleotide-binding domain (NBD) at the ..
  42. Elbatsh A, Haarhuis J, Petela N, Chapard C, Fish A, Celie P, et al. Cohesin Releases DNA through Asymmetric ATPase-Driven Ring Opening. Mol Cell. 2016;61:575-588 pubmed publisher
    ..To do so, cohesin must be protected against its cellular antagonist Wapl. Eco1 acetylates cohesin's Smc3 subunit, which locks together the sister DNAs...
  43. Kulemzina I, Ang K, Zhao X, Teh J, Verma V, Suranthran S, et al. A Reversible Association between Smc Coiled Coils Is Regulated by Lysine Acetylation and Is Required for Cohesin Association with the DNA. Mol Cell. 2016;63:1044-54 pubmed publisher
    ..Most of the ring circumference is comprised of the anti-parallel intramolecular coiled coils of the Smc1 and Smc3 proteins, which connect globular head and hinge domains...
  44. Huber R, Kulemzina I, Ang K, Chavda A, Suranthran S, Teh J, et al. Impairing Cohesin Smc1/3 Head Engagement Compensates for the Lack of Eco1 Function. Structure. 2016;24:1991-1999 pubmed publisher
    The cohesin ring, which is composed of the Smc1, Smc3, and Scc1 subunits, topologically embraces two sister chromatids from S phase until anaphase to ensure their precise segregation to the daughter cells...
  45. Hamza A, Baetz K. Iron-responsive transcription factor Aft1 interacts with kinetochore protein Iml3 and promotes pericentromeric cohesin. J Biol Chem. 2012;287:4139-47 pubmed publisher
    ..Our work defines a new role for Aft1 in chromosome stability and transmission. ..
  46. Chan K, Gligoris T, Upcher W, Kato Y, Shirahige K, Nasmyth K, et al. Pds5 promotes and protects cohesin acetylation. Proc Natl Acad Sci U S A. 2013;110:13020-5 pubmed publisher
    Cohesin's Smc1 and Smc3 subunits form V-shaped heterodimers, the nucleotide binding domains (NBDs) of which bind the C- and N-terminal domains, respectively, of the α-kleisin subunit, forming a large tripartite ring within in which ..
  47. Shivaraju M, Camahort R, Mattingly M, Gerton J. Scm3 is a centromeric nucleosome assembly factor. J Biol Chem. 2011;286:12016-23 pubmed publisher
    ..The centromere targeting domain of Cse4 is sufficient for Scm3 nucleosome assembly activity. Assembly does not depend on centromeric sequence. We propose that Scm3 plays an active role in centromeric nucleosome assembly. ..
  48. Katis V, Lipp J, Imre R, Bogdanova A, Okaz E, Habermann B, et al. Rec8 phosphorylation by casein kinase 1 and Cdc7-Dbf4 kinase regulates cohesin cleavage by separase during meiosis. Dev Cell. 2010;18:397-409 pubmed publisher
    ..Our data suggest that PP2A protects centromeric cohesion by opposing CK1delta/epsilon- and DDK-dependent phosphorylation of Rec8. ..
  49. McLellan J, O Neil N, Tarailo S, Stoepel J, Bryan J, Rose A, et al. Synthetic lethal genetic interactions that decrease somatic cell proliferation in Caenorhabditis elegans identify the alternative RFC CTF18 as a candidate cancer drug target. Mol Biol Cell. 2009;20:5306-13 pubmed publisher
    ..elegans. Furthermore, the C. elegans assay system will contribute to our knowledge of genetic interactions in a multicellular animal and is a powerful approach to identify new cancer therapeutic targets. ..
  50. Guacci V, Stricklin J, Bloom M, Guō X, Bhatter M, Koshland D. A novel mechanism for the establishment of sister chromatid cohesion by the ECO1 acetyltransferase. Mol Biol Cell. 2015;26:117-33 pubmed publisher ECO1 promotes cohesion, we conducted a genetic screen and identified a cohesion activator mutation in the SMC3 head domain (D1189H)...