Structural Maintenance of Chromosomes Complexes.

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  • Author(s): Jeppsson K;Jeppsson K;Jeppsson K
  • Source:
    Methods in molecular biology (Clifton, N.J.) [Methods Mol Biol] 2025; Vol. 2856, pp. 11-22.
  • Publication Type:
    Journal Article; Review
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Humana Press Country of Publication: United States NLM ID: 9214969 Publication Model: Print Cited Medium: Internet ISSN: 1940-6029 (Electronic) Linking ISSN: 10643745 NLM ISO Abbreviation: Methods Mol Biol Subsets: MEDLINE
    • Publication Information:
      Publication: Totowa, NJ : Humana Press
      Original Publication: Clifton, N.J. : Humana Press,
    • Subject Terms:
    • Abstract:
      The Structural Maintenance of Chromosomes (SMC) protein complexes are DNA-binding molecular machines required to shape chromosomes into functional units and to safeguard the genome through cell division. These ring-shaped multi-subunit protein complexes, which are present in all kingdoms of life, achieve this by organizing chromosomes in three-dimensional space. Mechanistically, the SMC complexes hydrolyze ATP to either stably entrap DNA molecules within their lumen, or rapidly reel DNA into large loops, which allow them to link two stretches of DNA in cis or trans. In this chapter, the canonical structure of the SMC complexes is first introduced, followed by a description of the composition and general functions of the main types of eukaryotic and prokaryotic SMC complexes. Thereafter, the current model for how SMC complexes perform in vitro DNA loop extrusion is presented. Lastly, chromosome loop formation by SMC complexes is introduced, and how the DNA loop extrusion mechanism contributes to chromosome looping by SMC complexes in cells is discussed.
      (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)
    • References:
      Yatskevich S, Rhodes J, Nasmyth K (2019) Organization of chromosomal DNA by SMC complexes. Annu Rev Genet 53:445–482. https://doi.org/10.1146/annurev-genet-112618-043633. (PMID: 10.1146/annurev-genet-112618-04363331577909)
      Oldenkamp R, Rowland BD (2022) A walk through the SMC cycle: from catching DNAs to shaping the genome. Mol Cell 82(9):1616–1630. https://doi.org/10.1016/j.molcel.2022.04.006. (PMID: 10.1016/j.molcel.2022.04.00635477004)
      Hirano T (2016) Condensin-based chromosome organization from bacteria to vertebrates. Cell 164(5):847–857. https://doi.org/10.1016/j.cell.2016.01.033. (PMID: 10.1016/j.cell.2016.01.03326919425)
      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. https://doi.org/10.1093/nar/gkae103.
      Jeppsson K, Pradhan B, Sutani T, Sakata T, Umeda Igarashi M, Berta DG, Kanno T, Nakato R, Shirahige K, Kim E, Bjorkegren C (2024) Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils. Mol Cell. https://doi.org/10.1016/j.molcel.2024.01.005.
      Gruber S (2018) SMC complexes sweeping through the chromosome: going with the flow and against the tide. Curr Opin Microbiol 42:96–103. https://doi.org/10.1016/j.mib.2017.10.004. (PMID: 10.1016/j.mib.2017.10.00429182912)
      Petrushenko ZM, She W, Rybenkov VV (2011) A new family of bacterial condensins. Mol Microbiol 81(4):881–896. https://doi.org/10.1111/j.1365-2958.2011.07763.x. (PMID: 10.1111/j.1365-2958.2011.07763.x217521073179180)
      Liu HW, Roisne-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. e4726. https://doi.org/10.1016/j.molcel.2022.11.015. (PMID: 10.1016/j.molcel.2022.11.01536525956)
      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. e4147. https://doi.org/10.1016/j.molcel.2022.09.008. (PMID: 10.1016/j.molcel.2022.09.008362067659637719)
      Decorsiere A, Mueller H, van Breugel PC, Abdul F, Gerossier L, Beran RK, Livingston CM, Niu C, Fletcher SP, Hantz O, Strubin M (2016) Hepatitis B virus X protein identifies the Smc5/6 complex as a host restriction factor. Nature 531(7594):386–389. https://doi.org/10.1038/nature17170. (PMID: 10.1038/nature1717026983541)
      Pradhan B, Kanno T, Umeda Igarashi M, Loke MS, Baaske MD, Wong JSK, Jeppsson K, Bjorkegren C, Kim E (2023) The Smc5/6 complex is a DNA loop-extruding motor. Nature 616(7958):843–848. https://doi.org/10.1038/s41586-023-05963-3. (PMID: 10.1038/s41586-023-05963-33707662610132971)
      Pradhan B, Deep A, Koenig J, Baaske M, Corbett K, Kim E (2024) Loop extrusion-mediated plasmid DNA cleavage by the bacterial SMC Wadjet complex. bioRxiv. https://doi.org/10.1101/2024.02.17.580791.
      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. https://doi.org/10.1126/science.aar7831. (PMID: 10.1126/science.aar7831294724436329450)
      Kim Y, Shi Z, Zhang H, Finkelstein IJ, Yu H (2019) Human cohesin compacts DNA by loop extrusion. Science 366(6471):1345–1349. https://doi.org/10.1126/science.aaz4475. (PMID: 10.1126/science.aaz4475317806277387118)
      Davidson IF, Bauer B, Goetz D, Tang W, Wutz G, Peters JM (2019) DNA loop extrusion by human cohesin. Science 366(6471):1338–1345. https://doi.org/10.1126/science.aaz3418. (PMID: 10.1126/science.aaz341831753851)
      Peng XP, Zhao X (2023) The multi-functional Smc5/6 complex in genome protection and disease. Nat Struct Mol Biol 30(6):724–734. https://doi.org/10.1038/s41594-023-01015-6. (PMID: 10.1038/s41594-023-01015-63733699410372777)
      Piche J, Van Vliet PP, Puceat M, Andelfinger G (2019) The expanding phenotypes of cohesinopathies: one ring to rule them all! Cell Cycle 18(21):2828–2848. https://doi.org/10.1080/15384101.2019.1658476. (PMID: 10.1080/15384101.2019.1658476315160826791706)
      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, Deciphering Developmental Disorders S, 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. https://doi.org/10.1101/gad.286351.116. (PMID: 10.1101/gad.286351.116277379595088565)
      Burmann F, Lowe J (2023) Structural biology of SMC complexes across the tree of life. Curr Opin Struct Biol 80:102598. https://doi.org/10.1016/j.sbi.2023.102598. (PMID: 10.1016/j.sbi.2023.1025983710497610512200)
      Dekker C, Haering CH, Peters JM, Rowland BD (2023) How do molecular motors fold the genome? Science 382(6671):646–648. https://doi.org/10.1126/science.adi8308. (PMID: 10.1126/science.adi830837943927)
      Michaelis C, Ciosk R, Nasmyth K (1997) Cohesins: chromosomal proteins that prevent premature separation of sister chromatids. Cell 91(1):35–45. https://doi.org/10.1016/s0092-8674(01)80007-6. (PMID: 10.1016/s0092-8674(01)80007-69335333)
      Guacci V, Koshland D, Strunnikov A (1997) A direct link between sister chromatid cohesion and chromosome condensation revealed through the analysis of MCD1 in S. cerevisiae. Cell 91(1):47–57. https://doi.org/10.1016/s0092-8674(01)80008-8. (PMID: 10.1016/s0092-8674(01)80008-893353342670185)
      Petela NJ, Gligoris TG, Metson J, Lee BG, Voulgaris M, Hu B, Kikuchi S, Chapard C, Chen W, Rajendra E, Srinivisan M, Yu H, Lowe J, Nasmyth KA (2018) Scc2 is a potent activator of cohesin’s ATPase that promotes loading by binding Scc1 without Pds5. Mol Cell 70(6):1134–1148. e1137. https://doi.org/10.1016/j.molcel.2018.05.022. (PMID: 10.1016/j.molcel.2018.05.022299329046028919)
      Hoencamp C, Rowland BD (2023) Genome control by SMC complexes. Nat Rev Mol Cell Biol 24(9):633–650. https://doi.org/10.1038/s41580-023-00609-8. (PMID: 10.1038/s41580-023-00609-837231112)
      Rao SSP, Huang SC, Glenn St Hilaire B, Engreitz JM, Perez EM, Kieffer-Kwon KR, Sanborn AL, Johnstone SE, Bascom GD, Bochkov ID, Huang X, Shamim MS, Shin J, Turner D, Ye Z, Omer AD, Robinson JT, Schlick T, Bernstein BE, Casellas R, Lander ES, Aiden EL (2017) Cohesin loss eliminates all loop domains. Cell 171(2):305–320.e324. https://doi.org/10.1016/j.cell.2017.09.026. (PMID: 10.1016/j.cell.2017.09.026289855625846482)
      Rao SS, Huntley MH, Durand NC, Stamenova EK, Bochkov ID, Robinson JT, Sanborn AL, Machol I, Omer AD, Lander ES, Aiden EL (2014) A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159(7):1665–1680. https://doi.org/10.1016/j.cell.2014.11.021. (PMID: 10.1016/j.cell.2014.11.021254975475635824)
      Nora EP, Goloborodko A, Valton AL, Gibcus JH, Uebersohn A, Abdennur N, Dekker J, Mirny LA, Bruneau BG (2017) Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization. Cell 169(5):930–944. e922. https://doi.org/10.1016/j.cell.2017.05.004. (PMID: 10.1016/j.cell.2017.05.004285257585538188)
      Costantino L, Hsieh TS, Lamothe R, Darzacq X, Koshland D (2020) Cohesin residency determines chromatin loop patterns. Elife 9. https://doi.org/10.7554/eLife.59889.
      Garcia-Luis J, Lazar-Stefanita L, Gutierrez-Escribano P, Thierry A, Cournac A, Garcia A, Gonzalez S, Sanchez M, Jarmuz A, Montoya A, Dore M, Kramer H, Karimi MM, Antequera F, Koszul R, Aragon L (2019) FACT mediates cohesin function on chromatin. Nat Struct Mol Biol 26(10):970–979. https://doi.org/10.1038/s41594-019-0307-x. (PMID: 10.1038/s41594-019-0307-x315828546779571)
      Jeppsson K, Sakata T, Nakato R, Milanova S, Shirahige K, Bjorkegren C (2022) Cohesin-dependent chromosome loop extrusion is limited by transcription and stalled replication forks. Sci Adv 8(23):eabn7063. https://doi.org/10.1126/sciadv.abn7063. (PMID: 10.1126/sciadv.abn7063356876829187231)
      Schwarzer W, Abdennur N, Goloborodko A, Pekowska A, Fudenberg G, Loe-Mie Y, Fonseca NA, Huber W, Haering CH, Mirny L, Spitz F (2017) Two independent modes of chromatin organization revealed by cohesin removal. Nature 551(7678):51–56. https://doi.org/10.1038/nature24281. (PMID: 10.1038/nature24281290946995687303)
      Haarhuis JHI, van der Weide RH, Blomen VA, Yanez-Cuna JO, Amendola M, van Ruiten MS, Krijger PHL, Teunissen H, Medema RH, van Steensel B, Brummelkamp TR, de Wit E, Rowland BD (2017) The cohesin release factor WAPL restricts chromatin loop extension. Cell 169(4):693–707. e614. https://doi.org/10.1016/j.cell.2017.04.013. (PMID: 10.1016/j.cell.2017.04.013284758975422210)
      Hirano T, Kobayashi R, Hirano M (1997) Condensins, chromosome condensation protein complexes containing XCAP-C, XCAP-E and a Xenopus homolog of the Drosophila Barren protein. Cell 89(4):511–521. https://doi.org/10.1016/s0092-8674(00)80233-0. (PMID: 10.1016/s0092-8674(00)80233-09160743)
      Hirano T, Mitchison TJ (1994) A heterodimeric coiled-coil protein required for mitotic chromosome condensation in vitro. Cell 79(3):449–458. https://doi.org/10.1016/0092-8674(94)90254-2. (PMID: 10.1016/0092-8674(94)90254-27954811)
      Shintomi K, Takahashi TS, Hirano T (2015) Reconstitution of mitotic chromatids with a minimum set of purified factors. Nat Cell Biol 17(8):1014–1023. https://doi.org/10.1038/ncb3187. (PMID: 10.1038/ncb318726075356)
      Gibcus JH, Samejima K, Goloborodko A, Samejima I, Naumova N, Nuebler J, Kanemaki MT, Xie L, Paulson JR, Earnshaw WC, Mirny LA, Dekker J (2018) A pathway for mitotic chromosome formation. Science 359(6376). https://doi.org/10.1126/science.aao6135.
      Kinoshita K, Tsubota Y, Tane S, Aizawa Y, Sakata R, Takeuchi K, Shintomi K, Nishiyama T, Hirano T (2022) A loop extrusion-independent mechanism contributes to condensin I-mediated chromosome shaping. J Cell Biol 221(3). https://doi.org/10.1083/jcb.202109016.
      Csankovszki G, Collette K, Spahl K, Carey J, Snyder M, Petty E, Patel U, Tabuchi T, Liu H, McLeod I, Thompson J, Sarkeshik A, Yates J, Meyer BJ, Hagstrom K (2009) Three distinct condensin complexes control C. elegans chromosome dynamics. Curr Biol 19(1):9–19. https://doi.org/10.1016/j.cub.2008.12.006. (PMID: 10.1016/j.cub.2008.12.006191190112682549)
      Albritton SE, Ercan S (2018) Caenorhabditis elegans dosage compensation: insights into condensin-mediated gene regulation. Trends Genet 34(1):41–53. https://doi.org/10.1016/j.tig.2017.09.010. (PMID: 10.1016/j.tig.2017.09.01029037439)
      Kim J, Jimenez DS, Ragipani B, Zhang B, Street LA, Kramer M, Albritton SE, Winterkorn LH, Morao AK, Ercan S (2022) Condensin DC loads and spreads from recruitment sites to create loop-anchored TADs in C. elegans. Elife 11. https://doi.org/10.7554/eLife.68745.
      Abdul F, Diman A, Baechler B, Ramakrishnan D, Kornyeyev D, Beran RK, Fletcher SP, Strubin M (2022) Smc5/6 silences episomal transcription by a three-step function. Nat Struct Mol Biol 29(9):922–931. https://doi.org/10.1038/s41594-022-00829-0. (PMID: 10.1038/s41594-022-00829-036097294)
      Aurélie D, Panis G, Castrogiovanni C, Prados J, Baechler B, Strubin M (2023) Human Smc5/6 recognises transcription-generated positive DNA supercoils. bioRxiv. https://doi.org/10.1101/2023.05.04.539344.
      Yoshinaga M, Inagaki Y (2021) Ubiquity and origins of structural maintenance of chromosomes (SMC) proteins in eukaryotes. Genome Biol Evol 13(12). https://doi.org/10.1093/gbe/evab256.
      Nasmyth K (2001) Disseminating the genome: joining, resolving, and separating sister chromatids during mitosis and meiosis. Annu Rev Genet 35:673–745. https://doi.org/10.1146/annurev.genet.35.102401.091334. (PMID: 10.1146/annurev.genet.35.102401.09133411700297)
      Barth R, Davidson I, van der Torre J, Taschner M, Gruber S, Peters JM, Dekker C (2023) SMC motor proteins extrude DNA asymmetrically and contain a direction switch. bioRxiv:2023-12.
      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. https://doi.org/10.1126/science.abm4012. (PMID: 10.1126/science.abm401235653469)
      Pradhan B, Barth R, Kim E, Davidson IF, Bauer B, van Laar T, Yang W, Ryu JK, van der Torre J, Peters JM, Dekker C (2022) SMC complexes can traverse physical roadblocks bigger than their ring size. Cell Rep 41(3):111491. https://doi.org/10.1016/j.celrep.2022.111491. (PMID: 10.1016/j.celrep.2022.11149136261017)
      Barth R, Pradhan B, Kim E, Davidson IF, van der Torre J, Peters JM, Dekker C (2023) Testing pseudotopological and nontopological models for SMC-driven DNA loop extrusion against roadblock-traversal experiments. Sci Rep 13(1):8100. https://doi.org/10.1038/s41598-023-35359-2. (PMID: 10.1038/s41598-023-35359-23720837410199080)
      Gabriele M, Brandao HB, Grosse-Holz S, Jha A, Dailey GM, Cattoglio C, Hsieh TS, Mirny L, Zechner C, Hansen AS (2022) Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging. Science 376(6592):496–501. https://doi.org/10.1126/science.abn6583. (PMID: 10.1126/science.abn6583354208909069445)
      Kong M, Cutts EE, Pan D, Beuron F, Kaliyappan T, Xue C, Morris EP, Musacchio A, Vannini A, Greene EC (2020) Human condensin I and II drive extensive ATP-dependent compaction of nucleosome-bound DNA. Mol Cell 79(1):99–114 e119. https://doi.org/10.1016/j.molcel.2020.04.026. (PMID: 10.1016/j.molcel.2020.04.026324456207335352)
      Kim E, Kerssemakers J, Shaltiel IA, Haering CH, Dekker C (2020) DNA-loop extruding condensin complexes can traverse one another. Nature 579(7799):438–442. https://doi.org/10.1038/s41586-020-2067-5. (PMID: 10.1038/s41586-020-2067-532132705)
      Davidson IF, Peters JM (2021) Genome folding through loop extrusion by SMC complexes. Nat Rev Mol Cell Biol 22(7):445–464. https://doi.org/10.1038/s41580-021-00349-7. (PMID: 10.1038/s41580-021-00349-733767413)
      Davidson IF, Barth R, Zaczek M, van der Torre J, Tang W, Nagasaka K, Janissen R, Kerssemakers J, Wutz G, Dekker C, Peters JM (2023) CTCF is a DNA-tension-dependent barrier to cohesin-mediated loop extrusion. Nature 616(7958):822–827. https://doi.org/10.1038/s41586-023-05961-5. (PMID: 10.1038/s41586-023-05961-53707662010132984)
      Zhang H, Shi Z, Banigan EJ, Kim Y, Yu H, Bai XC, Finkelstein IJ (2023) CTCF and R-loops are boundaries of cohesin-mediated DNA looping. Mol Cell 83(16):2856–2871 e2858. https://doi.org/10.1016/j.molcel.2023.07.006. (PMID: 10.1016/j.molcel.2023.07.00637536339)
      Banigan EJ, Tang W, van den Berg AA, Stocsits RR, Wutz G, Brandao HB, Busslinger GA, Peters JM, Mirny LA (2023) Transcription shapes 3D chromatin organization by interacting with loop extrusion. Proc Natl Acad Sci USA 120(11):e2210480120. https://doi.org/10.1073/pnas.2210480120. (PMID: 10.1073/pnas.22104801203689796910089175)
      Roisne-Hamelin F, Liu HW, Taschner M, Li Y, Gruber S (2024) Structural basis for plasmid restriction by SMC JET nuclease. Mol Cell. https://doi.org/10.1016/j.molcel.2024.01.009.
      Haering CH, Farcas AM, Arumugam P, Metson J, Nasmyth K (2008) The cohesin ring concatenates sister DNA molecules. Nature 454(7202):297–301. https://doi.org/10.1038/nature07098. (PMID: 10.1038/nature0709818596691)
      Guérin TM, Barrington C, Pobegalov G, Molodtsov MI, Uhlmann F (2023) Cohesin chromatin loop formation by an extrinsic motor. bioRxiv. https://doi.org/10.1101/2023.11.30.569410.
    • Contributed Indexing:
      Keywords: Chromosome loops; Cohesin; Condensin; Genome organization; Loop extrusion; SMC complexes; Smc5/6; Topological entrapment; Wadjet
    • Accession Number:
      0 (Multiprotein Complexes)
      0 (Cell Cycle Proteins)
      9007-49-2 (DNA)
      0 (Chromosomal Proteins, Non-Histone)
      8L70Q75FXE (Adenosine Triphosphate)
      0 (DNA-Binding Proteins)
    • Publication Date:
      Date Created: 20240916 Date Completed: 20240916 Latest Revision: 20241101
    • Publication Date:
      20241102
    • Accession Number:
      10.1007/978-1-0716-4136-1_2
    • Accession Number:
      39283444