Biology:SMC protein

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SMC proteins represent a large family of ATPases that participate in many aspects of higher-order chromosome organization and dynamics. SMC proteins are widely conserved across bacteria, archaea, and eukaryotes. In eukaryotes, they function as the core ATPase subunits of large protein complexes such as condensin, cohesin, and SMC5/6.[1][2][3][4]

The term SMC derives from a mutant strain of Saccharomyces cerevisiae named smc1 (stability of mini-chromosomes 1), which was identified based on its defect in maintaining the stability of mini-chromosomes.[5] After the gene product of SMC1 was characterized,[6] and homologous proteins were found to be essential for chromosome structure and dynamics in many organisms, the acronym SMC was redefined to stand for "Structural Maintenance of Chromosomes".[7]

Classification

Eukaryotic SMCs

Eukaryotes have at least six SMC proteins in individual organisms, and they form three distinct heterodimers with specialized functions:

  • SMC1-SMC3: A pair of SMC1 and SMC3 constitutes the core subunits of the cohesin complexes involved in sister chromatid cohesion.[8][9][10]
  • SMC5-SMC6: A pair of SMC5 and SMC6 functions as part of a yet-to-be-named complex implicated in DNA repair and checkpoint responses.[14]
Figure 1. Evolution of SMC proteins: SMCc, canonical SMC; SMCnc, non-canonical SMC; SMC14, ancestor of SMC1 & SMC4; SMC23, ancestor of SMC2 & SMC3; SMC556, ancestor of SMC5 & SMC6

The pairings of SMC proteins in eukaryotes, SMC1-SMC3, SMC2–SMC4, and SMC5–SMC6, are highly specific and invariant; no exceptions to these combinations have been reported to date. Sequence comparisons reveal that SMC1 and SMC4, as well as SMC2 and SMC3, share a high degree of similarity, while SMC5 and SMC6 form a more distinct clade (Figure 1).[15] It is hypothesized that the last eukaryotic common ancestor (LECA) possessed all six SMC proteins. While SMC1–4 are conserved in all known eukaryotic species, some lineages (such as the ciliate Tetrahymena thermophila) have lost SMC5 and SMC6 during evolution,[16][17] suggesting that the SMC5/6 complex may not be strictly essential for eukaryotic cell viability.

In addition to the six subtypes, some organisms have variants of SMC proteins. For instance, mammals have a meiosis-specific variant of SMC1, known as SMC1β.[18] The nematode Caenorhabditis elegans has an SMC4-variant that has a specialized role in dosage compensation.[19]

The following table shows the SMC proteins names for several model organisms and vertebrates:[20]

Subfamily Complex Vertebrates D. melanogaster C. elegans S. cerevisiae S. pombe T. thermophila
SMC1α cohesin SMC1α[10] Smc1 SMC-1 Smc1[6] Psm1 Smc1
SMC2 condensin SMC2/CAP-E[11][21] Smc2 MIX-1[22] Smc2[7] Cut14[23] Smc2
SMC3 cohesin SMC3[10] Smc3 SMC-3 Smc3[8] Psm3 Smc3
SMC4 condensin SMC4/CAP-C[11] Smc4 SMC-4 Smc4 Cut3[23] Smc4
SMC5 SMC5/6 SMC5 Smc5 SMC-5 Smc5 Smc5 -
SMC6 SMC5/6 SMC6 Smc6 SMC-6 Smc6 Smc6/Rad18[24] -
SMC1β cohesin（meiotic） SMC1β[18] - - - - -
SMC4 variant condensin IDC - - DPY-27[19] - - -

Prokaryotic SMCs

The evolutionary origin of SMC proteins is ancient, and homologs are widely conserved in both bacteria and archaea.[16]

  • SMC (canonical type): Many bacteria (e.g., Bacillus subtilis) and archaea possess canonical SMC proteins that closely resemble their eukaryotic counterparts.[25] These bacterial and archaeal SMCs form homodimers and associate with regulatory subunits to form condensin-like complexes, SMC-ScpAB. It is hypothesized that the eukaryotic ancestor (most likely the Asgard archaeon) possessed two types of SMC proteins: a canonical SMC (SMCc) and a non-canonical SMC (SMCnc). Gene duplications of these two ancestral types are thought to have given rise to the six SMC subfamilies present in the last eukaryotic common ancestor (LECA): SMC1–4 evolved from the canonical lineage, while SMC5 and SMC6 evolved from the non-canonical lineage (Figure 1).[16]
  • MukB: In some γ-proteobacteria, including Escherichia coli, SMC function is carried out by a distantly related protein called MukB.[26] MukB also forms homodimers and, together with regulatory subunits, assembles into a MukBEF complex, which performs condensin-like functions in organizing bacterial chromosomes.
  • MksB/JetC/EptC: A third type of prokaryotic SMC protein, known as MksB, has been identified in certain bacterial species. Like MukB, MksB forms a distantly-related condensin-like complex, MksBEF.[27] More recently, a variant complex called MksBEFG, which includes a nuclease subunit MksG, has been shown to function in plasmid defense.[28][29] In other bacterial lineages, orthologous systems have been identified, including JetABCD[30][31] and EptABCD.[32] These systems are collectively referred to as the Wadjet family of SMC-like complexes.

In a broader sense, several proteins with structural similarities to SMC are considered members of the SMC superfamily.

  • In eukaryotes, Rad50 is a well-known SMC-related protein involved in the repair of DNA double-strand breaks.[33]
  • In bacteria, several proteins related to DNA repair also belong to the extended SMC family, including SbcC,[34] RecF,[35] and RecN.[36]
  • In archaea, a subfamily known as Archaea-specific SMC-related proteins (ASRPs) has been identified.[37] Previously described archaeal proteins such as Sph1/2 [38] and ClsN (also known as coalescin) [39][40] are now considered members of this ASRP subfamily.

Subunit composition of SMC protein complexes

The subunit composition of SMC protein complexes varies across domains of life. The table below and Figures 2 & 3 summarize the representative complexes found in eukaryotes and prokaryotes.

Subunit type cohesin condensin I condensin II SMC5/6 SMC-ScpAB MukBEF JetABCD
ν-SMC SMC3 SMC2 SMC2 SMC5 SMC MukB JetC
κ-SMC SMC1 SMC4 SMC4 SMC6 SMC MukB JetC
kleisin RAD21 CAP-H CAP-H2 Nse4 ScpA MukF JetA
HEAT-A NIPBL/Pds5 CAP-D2 CAP-D3 - - - -
HEAT-B STAG1/2 CAP-G CAP-G2 - - - -
kite-A - - - Nse1 ScpB MukE JetB
kite-B - - - Nse3 ScpB MukE JetB
SUMO ligase - - - Nse2 - - -
nuclease - - - - - - JetD
Figure 2. Eukaryotic SMC complexes
Figure 3. Prokaryotic SMC complexes

All SMC dimers, whether of eukaryotic or prokaryotic origin, associate with a kleisin subunit. In condensins and cohesin, the kleisin subunit is further associated with a pair of HEAT-repeat subunits.[41] Notably, the eukaryotic SMC5/6 complex contains "kite" (kleisin interacting tandem winged-helix elements) subunits[42] instead of HEAT-repeat subunits,[41] making it structurally more similar to prokaryotic complexes such as SMC–ScpAB, MukBEF, and MksBEF. However, unlike their typically homodimeric prokaryotic counterparts, both the SMC and kite subunits in the SMC5/6 complex are heterodimeric, resulting in a more elaborate subunit architecture. The SMC5/6 complex and the Wadjet complex (JetABCD) each possess an additional catalytic subunit: the SUMO ligase Nse2 in SMC5/6,[43] and the nuclease JetD in JetABCD.[30][31]

Molecular structure

Figure 4. Basic structure of an SMC protein complex

Primary structure

SMC proteins are 1,000-1,500 amino-acid long. They have a modular structure that is composed of the following domains:

  • Walker A ATP-binding motif
  • coiled-coil region I
  • hinge region
  • coiled-coil region II
  • Walker B ATP-binding motif; signature motif

Secondary and tertiary structure

SMC dimers form a V-shaped molecule with two long coiled-coil arms (Figure 4).[44][45] To make such a unique structure, an SMC protomer is self-folded through anti-parallel coiled-coil interactions, forming a rod-shaped molecule. At one end of the molecule, the N-terminal and C-terminal domains form an ATP-binding domain. The other end is called a hinge domain. Two protomers then dimerize through their hinge domains and assemble a V-shaped dimer.[46][47] The length of the coiled-coil arms is ~50 nm long. Such long "antiparallel" coiled coils are very rare and found only among SMC proteins (and their relatives such as Rad50). The ATP-binding domain of SMC proteins is structurally related to that of ABC transporters, a large family of transmembrane proteins that actively transport small molecules across cellular membranes. It is thought that the cycle of ATP binding and hydrolysis modulates the cycle of closing and opening of the V-shaped molecule. Still, the detailed mechanisms of action of SMC proteins remain to be determined.

Holo-complex assembly

The formation of an SMC protein complex involves the association of an SMC dimer with non-SMC subunits (Figure 4). First, the N-terminal domain of the kleisin subunit binds to the neck region (a segment of the coiled coil near the head domain) of one SMC protein,[48][49][50] while its C-terminal domain binds to the cap region (part of the head domain) of the other SMC subunit.[51][50] These interactions result in the formation of a ring-like architecture. As a consequence, the SMC–kleisin trimer adopts an asymmetric configuration. Accordingly, the SMC subunit bound at the N-terminal domain of the kleisin is sometimes referred to as the ν-SMC, while the one bound at the C-terminal domain is called the κ-SMC. Finally, two HEAT-repeat subunits (or two KITE subunits depending on the complex) associate with the central region of the kleisin, completing the assembly of the holo-complex. MukBEF and JetABC form higher-order assemblies through dimerization mediated by their kleisin subunits, a configuration often referred to as a "dimer-of-dimers" (Figure 3).

Molecular activities

SMC protein complexes are involved in a wide range of chromosome-related functions, and each complex is thought to possess distinct molecular activities tailored to its specific role. At the same time, based on their evolutionary origins and conserved structural features, it has been suggested that certain molecular activities may be shared across multiple SMC complexes.

For example, several SMC complexes are known to exhibit DNA entrapment activity, in which DNA is topologically entrapped within the ring-like structure formed by their long coiled-coil arms. This activity has been demonstrated in cohesin,[52][53] condensin,[54][55][56] and the SMC5/6 complex.[57]

More recent studies have highlighted DNA loop extrusion as a conserved molecular activity shared by many SMC protein complexes. Single-molecule analyses have demonstrated that condensin,[58] cohesin,[59][60] the SMC5/6 complex,[61] and Wadjet[62] are capable of extruding DNA loops in an ATP-dependent manner. During loop extrusion, the ATPase cycle of the SMC subunits is thought to be coupled with dynamic and multivalent interactions between various subunits and DNA. These interactions likely occur in multiple modes, making the molecular mechanism of loop extrusion highly complex and still incompletely understood.[63][64]

Genetic Disorders

Several genetic disorders have been linked to mutations in genes encoding components or regulators of SMC protein complexes:

International SMC meetings

Active research on SMC proteins began in the 1990s. As global interest in this field increased, international meetings dedicated to SMC proteins have been held regularly since the 2010s. These meetings, which are organized approximately every two years, cover a wide range of topics reflecting the diverse functions of SMC protein complexes, from bacterial chromosome segregation to human genetic disorders.

  • The 0th International SMC meeting（The 18th IMCB Symposium）"SMC proteins: from molecule to disease", November 29, 2013, Tokyo, Japan.
  • The 1st International SMC meeting（EMBO Workshop）"SMC proteins: chromosomal organizers from bacteria to human", May 12-15, 2015, Vienna, Austria.
  • The 2nd International SMC meeting[75] "SMC proteins: chromosomal organizers from bacteria to human", June 13-16, 2017, Nanyo, Yamagata, Japan.
  • The 3rd International SMC meeting[76]（EMBO Workshop）"Organization of bacterial and eukaryotic genomes by SMC complexes", September 10-13, 2019, Vienna, Austria.
  • The 4th International SMC meeting (Biochemical Society of the UK）"Genome Organisation by SMC protein complexes", September 27-30, 2022, Edinburgh, UK.
  • The 5th International SMC meeting[77][78]（NIG & RIKEN International Symposium 2024）"SMC complexes: orchestrating diverse genome functions", October 15-18, 2024, Numazu, Shizuoka, Japan.

See also

References

  1. ↑ Uhlmann F (2016). "SMC complexes: from DNA to chromosomes". Nat. Rev. Mol. Cell Biol. 17 (7): 399–412. doi:10.1038/nrm.2016.30. PMID 27075410. https://figshare.com/articles/journal_contribution/25913146. 
  2. ↑ Yatskevich S, Rhodes J, Nasmyth K (2019). "Organization of chromosomal DNA by SMC complexes". Annu. Rev. Genet. 53: 445–482. doi:10.1146/annurev-genet-112618-043633. PMID 31577909. 
  3. ↑ Peng XP, Zhao X (2023). "The multi-functional Smc5/6 complex in genome protection and disease". Nat Struct Mol Biol 30 (6): 724–734. doi:10.1038/s41594-023-01015-6. PMID 37336994. 
  4. ↑ Roy S, Adhikary H, D'Amours D (2024). "The SMC5/6 complex: folding chromosomes back into shape when genomes take a break". Nucleic Acids Res 52 (5): 2112–2129. doi:10.1093/nar/gkae103. PMID 38375830. 
  5. ↑ Larionov VL, Karpova TS, Kouprina NY, Jouravleva GA (1985). "A mutant of Saccharomyces cerevisiae with impaired maintenance of centromeric plasmids". Curr Genet 10 (1): 15–20. doi:10.1007/BF00418488. PMID 3940061. 
  6. ↑ 6.0 6.1 Strunnikov AV, Larionov VL, Koshland D (1993). "SMC1: an essential yeast gene encoding a putative head-rod-tail protein is required for nuclear division and defines a new ubiquitous protein family". J. Cell Biol. 123 (6 Pt 2): 1635–1648. doi:10.1083/jcb.123.6.1635. PMID 8276886. 
  7. ↑ 7.0 7.1 Strunnikov AV, Hogan E, Koshland D (1995). "SMC2, a Saccharomyces cerevisiae gene essential for chromosome segregation and condensation, defines a subgroup within the SMC family". Genes Dev 9 (5): 587–599. doi:10.1101/gad.9.5.587. PMID 7698648. 
  8. ↑ 8.0 8.1 "Cohesins: chromosomal proteins that prevent premature separation of sister chromatids". Cell 91 (1): 35–45. 1997. doi:10.1016/S0092-8674(01)80007-6. PMID 9335333. 
  9. ↑ "A direct link between sister chromatid cohesion and chromosome condensation revealed through the analysis of MCD1 in S. cerevisiae". Cell 91 (1): 47–57. 1998. doi:10.1016/S0092-8674(01)80008-8. PMID 9335334. 
  10. ↑ 10.0 10.1 10.2 "Identification of Xenopus SMC protein complexes required for sister chromatid cohesion". Genes Dev. 12 (13): 1986–1997. 1998. doi:10.1101/gad.12.13.1986. PMID 9649503. 
  11. ↑ 11.0 11.1 11.2 Hirano T, Mitchison TJ (1994). "A heterodimeric coiled-coil protein required for mitotic chromosome condensation in vitro". Cell 79 (3): 449–458. doi:10.1016/0092-8674(94)90254-2. PMID 7954811. 
  12. ↑ "Condensins, chromosome condensation complex containing XCAP-C, XCAP-E and a Xenopus homolog of the Drosophila Barren protein". Cell 89 (4): 511–21. 1997. doi:10.1016/S0092-8674(00)80233-0. PMID 9160743. 
  13. ↑ "Differential contributions of condensin I and condensin II to mitotic chromosome architecture in vertebrate cells". Cell 115 (1): 109–21. 2003. doi:10.1016/S0092-8674(03)00724-4. PMID 14532007. 
  14. ↑ "A novel SMC protein complex in Schizosaccharomyces pombe contains the Rad18 DNA repair protein". EMBO J. 19 (7): 1691–1702. 2000. doi:10.1093/emboj/19.7.1691. PMID 10747036. 
  15. ↑ Cobbe N, Heck MM (2004). "The evolution of SMC proteins: phylogenetic analysis and structural implications". Mol. Biol. Evol. 21 (2): 332–347. doi:10.1093/molbev/msh023. PMID 14660695. 
  16. ↑ 16.0 16.1 16.2 Yoshinaga M, Inagaki Y (2021). "Ubiquity and Origins of Structural Maintenance of Chromosomes (SMC) Proteins in Eukaryotes". Genome Biol Evol 13 (12). doi:10.1093/gbe/evab256. PMID 34894224. 
  17. ↑ van Hooff JJE, Raas MWD, Tromer EC, Eme L (2025). "Repeated duplications and losses shaped SMC complex evolution from archaeal ancestors to modern eukaryotes". Cell Rep 44 (7). doi:10.1016/j.celrep.2025.115855. PMID 40540396. 
  18. ↑ 18.0 18.1 "Novel meiosis-specific isoform of mammalian SMC1". Mol. Cell. Biol. 21 (20): 6984–6998. 2001. doi:10.1128/MCB.21.20.6984-6998.2001. PMID 11564881. 
  19. ↑ 19.0 19.1 "DPY-27:a chromosome condensation protein homolog that regulates C. elegans dosage compensation through association with the X chromosome". Cell 79 (3): 459–474. 1994. doi:10.1016/0092-8674(94)90255-0. PMID 7954812. 
  20. ↑ Schleiffer, Alexander; Kaitna, Susanne; Maurer-Stroh, Sebastian; Glotzer, Michael; Nasmyth, Kim; Eisenhaber, Frank (March 2003). "Kleisins: A Superfamily of Bacterial and Eukaryotic SMC Protein Partners". Molecular Cell 11 (3): 571–575. doi:10.1016/s1097-2765(03)00108-4. ISSN 1097-2765. PMID 12667442. 
  21. ↑ Saitoh N, Goldberg IG, Wood ER, Earnshaw WC (1994). "ScII: an abundant chromosome scaffold protein is a member of a family of putative ATPases with an unusual predicted tertiary structure". J Cell Biol 127 (2): 303–318. doi:10.1083/jcb.127.2.303. PMID 7929577. 
  22. ↑ Lieb JD, Albrecht MR, Chuang PT, Meyer BJ (1998). "MIX-1: an essential component of the C. elegans mitotic machinery executes X chromosome dosage compensation". Cell 92 (2): 265–277. doi:10.1016/s0092-8674(00)80920-4. PMID 9458050. 
  23. ↑ 23.0 23.1 Saka Y, Sutani T, Yamashita Y, Saitoh S, Takeuchi M, Nakaseko Y, Yanagida M (1994). "Fission yeast cut3 and cut14, members of a ubiquitous protein family, are required for chromosome condensation and segregation in mitosis". EMBO J 13 (20): 4938–4952. doi:10.1002/j.1460-2075.1994.tb06821.x. PMID 7957061. 
  24. ↑ Lehmann AR, Walicka M, Griffiths DJ, Murray JM, Watts FZ, McCready S, Carr AM (1995). "The rad18 gene of Schizosaccharomyces pombe defines a new subgroup of the SMC superfamily involved in DNA repair". Mol Cell Biol 15 (12): 7067–7080. doi:10.1128/MCB.15.12.7067. PMID 8524274. 
  25. ↑ Britton RA, Lin DC, Grossman AD (1998). "Characterization of a prokaryotic SMC protein involved in chromosome partitioning". Genes Dev. 12 (9): 1254–1259. doi:10.1101/gad.12.9.1254. PMID 9573042. 
  26. ↑ Niki H, Jaffé A, Imamura R, Ogura T, Hiraga S (1991). "The new gene mukB codes for a 177 kd protein with coiled-coil domains involved in chromosome partitioning of E. coli". EMBO J. 10 (1): 183–193. doi:10.1002/j.1460-2075.1991.tb07935.x. PMID 1989883. 
  27. ↑ Petrushenko ZM, She W, Rybenkov VV (2011). "A new family of bacterial condensins". Mol. Microbiol. 81 (4): 881–896. doi:10.1111/j.1365-2958.2011.07763.x. PMID 21752107. 
  28. ↑ Böhm K, Giacomelli G, Schmidt A, Imhof A, Koszul R, Marbouty M, Bramkamp M (2020). "Chromosome organization by a conserved condensin-ParB system in the actinobacterium Corynebacterium glutamicum". Nat Commun 11 (1): 1485. doi:10.1038/s41467-020-15238-4. PMID 32198399. Bibcode: 2020NatCo..11.1485B. 
  29. ↑ Weiß M, Giacomelli G, Assaya MB, Grundt F, Haouz A, Peng F, Petrella S, Wehenkel AM, Bramkamp M (2023). "The MksG nuclease is the executing part of the bacterial plasmid defense system MksBEFG". Nucl Acids Res 51 (7): 3288–3306. doi:10.1093/nar/gkad130. PMID 36881760. 
  30. ↑ 30.0 30.1 Deep A, Gu Y, Gao YQ, Ego KM, Herzik MA Jr, Zhou H, Corbett KD (2022). "The SMC-family Wadjet complex protects bacteria from plasmid transformation by recognition and cleavage of closed-circular DNA". Mol Cell 82 (21): 4145–4159.e7. doi:10.1016/j.molcel.2022.09.008. PMID 36206765. 
  31. ↑ 31.0 31.1 Liu HW, Roisné-Hamelin F, Beckert B, Li Y, Myasnikov A, Gruber S (2022). "DNA-measuring Wadjet SMC ATPases restrict smaller circular plasmids by DNA cleavage". Mol Cell 82 (24): 4727–4740.e6. doi:10.1016/j.molcel.2022.11.015. PMID 36525956. 
  32. ↑ Panas MW, Jain P, Yang H, Mitra S, Biswas D, Wattam AR, Letvin NL, Jacobs WR Jr (2014). "Noncanonical SMC protein in Mycobacterium smegmatis restricts maintenance of Mycobacterium fortuitum plasmids". Proc Natl Acad Sci USA 111 (37): 13264–13271. doi:10.1073/pnas.1414207111. PMID 25197070. Bibcode: 2014PNAS..11113264P. 
  33. ↑ Hopfner KP, Karcher A, Shin DS, Craig L, Arthur LM, Carney JP, Tainer JA (2000). "Structural biology of Rad50 ATPase: ATP-driven conformational control in DNA double-strand break repair and the ABC-ATPase superfamily". Cell 101 (7): 789–800. doi:10.1016/S0092-8674(00)80890-9. PMID 10892749. 
  34. ↑ Connelly JC, Kirkham LA, Leach DR (1998). "The SbcCD nuclease of Escherichia coli is a structural maintenance of chromosomes (SMC) family protein that cleaves hairpin DNA". Proc. Natl. Acad. Sci. USA 95 (14): 7969–7974. doi:10.1073/pnas.95.14.7969. PMID 9653124. Bibcode: 1998PNAS...95.7969C. 
  35. ↑ Michel-Marks E, Courcelle CT, Korolev S, Courcelle J (2010). "ATP binding, ATP hydrolysis, and protein dimerization are required for RecF to catalyze an early step in the processing and recovery of replication forks disrupted by DNA damage". J. Mol. Biol. 401 (4): 579–589. doi:10.1016/j.jmb.2010.06.013. PMID 20558179. 
  36. ↑ Pellegrino S, Radzimanowski J, de Sanctis D, Boeri Erba E, McSweeney S, Timmins J (2012). "Structural and functional characterization of an SMC-like protein RecN: new insights into double-strand break repair". Structure 20 (12): 2076–2089. doi:10.1016/j.str.2012.09.010. PMID 23085075. 
  37. ↑ Yoshinaga M, Nakayama T, Inagaki Y (2022). "A novel structural maintenance of chromosomes (SMC)-related protein family specific to Archaea". Front Microbiol 13. doi:10.3389/fmicb.2022.913088. PMID 35992648. 
  38. ↑ Herrmann U, Soppa J (2002). "Cell cycle-dependent expression of an essential SMC-like protein and dynamic chromosome localization in the archaeon Halobacterium salinarum". Mol Microbiol 46 (4): 895–906. doi:10.1046/j.1365-2958.2002.03181.x. PMID 12406217. 
  39. ↑ Takemata N, Samson RY, Bell SD (2019). "Physical and Functional Compartmentalization of Archaeal Chromosomes". Cell 179 (1): 165–179.e18. doi:10.1016/j.cell.2019.08.036. PMID 31539494. 
  40. ↑ Pilatowski-Herzing E, Samson RY, Takemata N, Badel C, Bohall PB, Bell SD (2025). "Capturing chromosome conformation in Crenarchaea". Mol Microbiol 123 (2): 101–108. doi:10.1111/mmi.15245. PMID 38404013. 
  41. ↑ 41.0 41.1 Yoshimura SH, Hirano T (2016). "HEAT repeats – versatile arrays of amphiphilic helices working in crowded environments?". J Cell Sci 129 (21): 3963–3970. doi:10.1242/jcs.185710. PMID 27802131. 
  42. ↑ Palecek JJ, Gruber S (2015). "Kite Proteins: a Superfamily of SMC/Kleisin Partners Conserved Across Bacteria, Archaea, and Eukaryotes". Structure 23 (12): 2183–2190. doi:10.1016/j.str.2015.10.004. PMID 26585514. 
  43. ↑ Andrews EA, Palecek J, Sergeant J, Taylor E, Lehmann AR, Watts FZ (2005). "Nse2, a component of the Smc5-6 complex, is a SUMO ligase required for the response to DNA damage". Mol Cell Biol 25 (1): 185–196. doi:10.1128/MCB.25.1.185-196.2005. PMID 15601841. 
  44. ↑ "The symmetrical structure of structural maintenance of chromosomes (SMC) and MukB proteins: long, antiparallel coiled coils, folded at a flexible hinge". J. Cell Biol. 142 (6): 1595–1604. 1998. doi:10.1083/jcb.142.6.1595. PMID 9744887. 
  45. ↑ "Condensin and cohesin display different arm conformations with characteristic hinge angles". J. Cell Biol. 156 (6): 419–424. 2002. doi:10.1083/jcb.200111002. PMID 11815634. 
  46. ↑ "Molecular architecture of SMC proteins and the yeast cohesin complex.". Mol. Cell 9 (4): 773–788. 2002. doi:10.1016/S1097-2765(02)00515-4. PMID 11983169. 
  47. ↑ "Hinge-mediated dimerization of SMC protein is essential for its dynamic interaction with DNA". EMBO J. 21 (21): 5733–5744. 2002. doi:10.1093/emboj/cdf575. PMID 12411491. 
  48. ↑ Bürmann F, Shin HC, Basquin J, Soh YM, Giménez-Oya V, Kim YG, Oh BH, Gruber S. (2013). "An asymmetric SMC-kleisin bridge in prokaryotic condensin". Nat. Struct. Mol. Biol. 20 (3): 371–379. doi:10.1038/nsmb.2488. PMID 23353789. 
  49. ↑ Gligoris TG, Scheinost JC, Bürmann F, Petela N, Chan KL, Uluocak P, Beckouët F, Gruber S, Nasmyth K, Löwe J. (2014). "Closing the cohesin ring: structure and function of its Smc3-kleisin interface". Science 346 (6212): 963–967. doi:10.1126/science.1256917. PMID 25414305. Bibcode: 2014Sci...346..963G. 
  50. ↑ 50.0 50.1 Hassler M, Shaltiel IA, Kschonsak M, Simon B, Merkel F, Thärichen L, Bailey HJ, Macošek J, Bravo S, Metz J, Hennig J, Haering CH (2019). "Structural basis of an asymmetric condensin ATPase cycle". Mol Cell 74 (6): 1175–1188.e24. doi:10.1016/j.molcel.2019.03.037. PMID 31226277. 
  51. ↑ Haering CH, Schoffnegger D, Nishino T, Helmhart W, Nasmyth K, Löwe J. (2004). "Structure and stability of cohesin's Smc1-kleisin interaction.". Mol. Cell 15 (6): 951–964. doi:10.1016/j.molcel.2004.08.030. PMID 15383284. 
  52. ↑ Haering CH, Farcas AM, Arumugam P, Metson J, Nasmyth K (2008). "The cohesin ring concatenates sister DNA molecules". Nature 454 (7202): 297–301. doi:10.1038/nature07098. PMID 18596691. Bibcode: 2008Natur.454..297H. http://wrap.warwick.ac.uk/207/1/WRAP_Arumugam_resubmitted_cover_delete.pdf. 
  53. ↑ Murayama Y, Uhlmann F (2014). "Biochemical reconstitution of topological DNA binding by the cohesin ring". Nature 505 (7483): 367–371. doi:10.1038/nature12867. PMID 24291789. Bibcode: 2014Natur.505..367M. 
  54. ↑ Cuylen S, Metz J, Haering CH (2011). "Condensin structures chromosomal DNA through topological links". Nat Struct Mol Biol 18 (8): 894–901. doi:10.1038/nsmb.2087. PMID 21765419. 
  55. ↑ Shaltiel IA, Datta S, Lecomte L, Hassler M, Kschonsak M, Bravo S, Stober C, Ormanns J, Eustermann S, Haering CH (2022). "A hold-and-feed mechanism drives directional DNA loop extrusion by condensin". Science 376 (6597): 1087–1094. doi:10.1126/science.abm4012. PMID 35653469. Bibcode: 2022Sci...376.1087S. 
  56. ↑ Tang M, Pobegalov G, Tanizawa H, Chen ZA, Rappsilber J, Molodtsov M, Noma KI, Uhlmann F (2023). "Establishment of dsDNA-dsDNA interactions by the condensin complex". Mol Cell 83 (21): 3787–3800.e9. doi:10.1016/j.molcel.2023.09.019. PMID 37820734. 
  57. ↑ Kanno T, Berta DG, Sjögren C (2015). "The Smc5/6 Complex Is an ATP-Dependent Intermolecular DNA Linker". Cell Rep 12 (9): 1471–1482. doi:10.1016/j.celrep.2015.07.048. PMID 26299966. 
  58. ↑ Ganji M, Shaltiel IA, Bisht S, Kim E, Kalichava A, Haering CH, Dekker C (2018). "Real-time imaging of DNA loop extrusion by condensin". Science 360 (6384): 102–105. doi:10.1126/science.aar7831. PMID 29472443. Bibcode: 2018Sci...360..102G. 
  59. ↑ Davidson IF, Bauer B, Goetz D, Tang W, Wutz G, Peters JM (2019). "DNA loop extrusion by human cohesin". Science 366 (6471): 1338–1345. doi:10.1126/science.aaz3418. PMID 31753851. Bibcode: 2019Sci...366.1338D. 
  60. ↑ Kim Y, Shi Z, Zhang H, Finkelstein IJ, Yu H (2019). "Human cohesin compacts DNA by loop extrusion". Science 366 (6471): 1345–1349. doi:10.1126/science.aaz4475. PMID 31780627. Bibcode: 2019Sci...366.1345K. 
  61. ↑ Pradhan B, Kanno T, Umeda Igarashi M, Loke MS, Baaske MD, Wong JSK, Jeppsson K, Björkegren C, Kim E (2023). "The Smc5/6 complex is a DNA loop-extruding motor". Nature 616 (7958): 843–848. doi:10.1038/s41586-023-05963-3. PMID 37076626. Bibcode: 2023Natur.616..843P. 
  62. ↑ Pradhan B, Deep A, König J, Baaske MD, Corbett KD, Kim E (2025). "Loop-extrusion-mediated plasmid DNA cleavage by the bacterial SMC Wadjet complex". Mol Cell 85 (1): 107–116.e5. doi:10.1016/j.molcel.2024.11.002. PMID 39626662. 
  63. ↑ Oldenkamp R, Rowland BD (2022). "A walk through the SMC cycle: From catching DNAs to shaping the genome". Mol Cell 82 (9): 1616–1630. doi:10.1016/j.molcel.2022.04.006. PMID 35477004. 
  64. ↑ Dekker C, Haering CH, Peters, JM, Rowland, BD (2023). "How do molecular motors fold the genome?". Science 382 (6671): 646–648. doi:10.1126/science.adi8308. PMID 37943927. Bibcode: 2023Sci...382..646D. http://resolver.tudelft.nl/uuid:7fc47989-1d98-40b1-ba87-3bd189025859. 
  65. ↑ Krantz ID, McCallum J, DeScipio C, Kaur M, Gillis LA, Yaeger D, Jukofsky L, Wasserman N, Bottani A, Morris CA, Nowaczyk MJM, Toriello H, Bamshad MJ, Carey JC, Rappaport E, Kawauchi S, Lander AD, Calof AL, Li HH, Devoto M, Jackson LG (2004). "Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B". Nat Genet 36 (6): 631–635. doi:10.1038/ng1364. PMID 15146186. 
  66. ↑ Tonkin ET, Wang TJ, Lisgo S, Bamshad MJ, Strachan T (2004). "NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome". Nat Genet 36 (6): 636–641. doi:10.1038/ng1363. PMID 15146185. 
  67. ↑ Deardorff MA, Kaur M, Yaeger D, Rampuria A, Korolev S, Pie J, Gil-Rodríguez C, Arnedo M, Loeys B, Kline AD, Wilson M, Lillquist K, Siu V, Ramos FJ, Musio A, Jackson LS, Dorsett D, Krantz ID (2007). "Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation". Am. J. Hum. Genet. 80 (3): 485–494. doi:10.1086/511888. PMID 17273969. 
  68. ↑ Vega H, Waisfisz Q, Gordillo M, Sakai N, Yanagihara I, Yamada M, van Gosliga D, Kayserili H, Xu C, Ozono K, Jabs EW, Inui K, Joenje H (2005). "Roberts syndrome is caused by mutations in ESCO2, a human homolog of yeast ECO1 that is essential for the establishment of sister chromatid cohesion". Nat Genet 37 (5): 468–470. doi:10.1038/ng1548. PMID 15821733. 
  69. ↑ Solomon DA, Kim T, Diaz-Martinez LA, Fair J, Elkahloun AG, Harris BT, Toretsky JA, Rosenberg SA, Shukla N, Ladanyi M, Samuels Y, James CD, Yu H, Kim JS, Waldman T (2011). "Mutational inactivation of STAG2 causes aneuploidy in human cancer". Science 333 (6045): 1039–1043. doi:10.1126/science.1203619. PMID 21852505. Bibcode: 2011Sci...333.1039S. 
  70. ↑ Scott JS, Al Ayadi L, Epeslidou E, van Scheppingen RH, Mukha A, Kaaij LJT, Lutz C, Prekovic S (2025). "Emerging roles of cohesin-STAG2 in cancer". Oncogene 44 (5): 277–287. doi:10.1038/s41388-024-03221-y. PMID 39613934. 
  71. ↑ Martin CA, Murray JE, Carroll P, Leitch A, Mackenzie KJ, Halachev M, Fetit AE, Keith C, Bicknell LS, Fluteau A, Gautier P, Hall EA, Joss S, Soares G, Silva J, Bober MB, Duker A, Wise CA, Quigley AJ, Phadke SR, The DDD Study, Wood AJ, Vagnarelli P, Jackson AP (2016). "Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis". Genes Dev 30 (19): 2158–2172. doi:10.1101/gad.286351.116. PMID 27737959. 
  72. ↑ Payne F, Colnaghi R, Rocha N, Seth A, Harris J, Carpenter G, Bottomley WE, Wheeler E, Wong S, Saudek V, Savage D, O'Rahilly S, Carel JC, Barroso I, O'Driscoll M, Semple R (2014). "Hypomorphism in human NSMCE2 linked to primordial dwarfism and insulin resistance". J Clin Invest 124 (9): 4028–4038. doi:10.1172/JCI73264. PMID 25105364. 
  73. ↑ van der Crabben SN, Henneman P, Brandsma AM, Thijssen PE, Hodzic Z, van Steensel MA, van den Berg S, van Es RM, de Winter JP, van den Berg TK, Santen GW, van Haaften G, Brunner HG, Kriek M, Monroe JG, Hennekam RC, Hoogerbrugge N, Kanaar R, van Attikum H, Majoor CJ, van der Burg M (2016). "Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease". J Clin Invest 126 (8): 2881–2892. doi:10.1172/JCI82890. PMID 27427983. 
  74. ↑ Grange LJ, Reynolds JJ, Ullah F, Isidor B, Shearer RF, Latypova X, Baxley RM, Oliver AW, Ganesh A, Cooke SL, Jhujh SS, McNee GS, Hollingworth R, Higgs MR, Natsume T, Khan T, Martos-Moreno GÁ, Chupp S, Mathew CG, Parry D, Simpson MA, Nahavandi N, Yüksel Z, Drasdo M, Kron A, Vogt P, Jonasson A, Seth SA, Gonzaga-Jauregui C, Brigatti KW, Stegmann APA, Kanemaki M, Josifova D, Uchiyama Y, Oh Y, Morimoto A, Osaka H, Ammous Z, Argente J, Matsumoto N, Stumpel CTRM, Taylor AMR, Jackson AP, Bielinsky AK, Mailand N, Le Caignec C, Davis EE, Stewart GS (2022). "Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy". Nat Commun 13 (1): 6664. doi:10.1038/s41467-022-34349-8. PMID 36333305. Bibcode: 2022NatCo..13.6664G. 
  75. ↑ Hirano T, Nishiyama T, Shirahige K (2017). "Hot debate in hot springs: Report on the second international meeting on SMC proteins". Genes to Cells 22 (11): 934–938. doi:10.1111/gtc.12539. PMID 29067760. 
  76. ↑ EMBO Workshop 2019
  77. ↑ NIG & RIKEN International Symposium 2024
  78. ↑ Niki H, Murayama Y (2025). "The Meeting Report on the Fifth International Conference of the Chromosomal SMC Complexes". Genes to Cells 30 (5). doi:10.1111/gtc.70039. PMID 40763930. 



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