Condensin

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An interphase nucleus (left) and a set of mitotic chromosomes (right) from human tissue culture cells. Bar, 10 μm.

Condensins are large protein complexes that play a central role in chromosome assembly and segregation during mitosis and meiosis.[1][2]

Subunit composition[edit]

Eukaryotic condensins[edit]

Subunit composition of condensin complexes

Many eukaryotic cells possess two different types of condensin complexes, known as condensin I and condensin II, each of which is composed of five subunits.[3][4] Condensins I and II share the same pair of core subunits, SMC2 and SMC4, both belonging to a large family of chromosomal ATPases, known as SMC proteins (SMC stands for Structural Maintenance of Chromosomes). Each of the complexes contains a distinct set of non-SMC regulatory subunits (a kleisin subunit[5] and a pair of HEAT-repeat subunits[6]). The nematode Caenorhabditis elegans possesses a third complex (closely related to condensin I) that participates in chromosome-wide gene regulation, i.e., dosage compensation.[7] In this complex, known as condensin IDC, the authentic SMC4 subunit is replaced with its variant, DPY-27.

Complex Subunit Classification S. cerevisiae S. pombe C. elegans D. melanogaster Vertebrates (human genes)
condensin I & II SMC2 ATPase Smc2 Cut14 MIX-1 DmSmc2 CAP-E (SMC2)
condensin I & II SMC4 ATPase Smc4 Cut3 SMC-4 DmSmc4 CAP-C (SMC4)
condensin I CAP-D2 HEAT Ycs4 Cnd1 DPY-28 CG1911 CAP-D2 (NCAPD2)
condensin I CAP-G HEAT Ycg1 Cnd3 CAP-G1 cap-g CAP-G (NCAPG)
condensin I CAP-H kleisin Brn1 Cnd2 DPY-26 barren CAP-H (NCAPH)
condensin II CAP-D3 HEAT - - HCP-6 CG31989 CAP-D3 (NCAPD3)
condensin II CAP-G2 HEAT - - CAP-G2 -? CAP-G2 (NCAPG2)
condensin II CAP-H2 kleisin - - KLE-2 CG14685 CAP-H2 (NCAPH2)
condensin IDC SMC4 variant ATPase - - DPY-27 - -

The structure and function of condensin I are conserved from yeast to humans, but yeast has no condensin II.[8][9] There is no apparent relationship between the occurrence of condensin II and the size of eukaryotic genomes. In fact, the primitive red alga Cyanidioschyzon merolae has both condensins I and II although its genome size is small and comparable to that of yeast.[10]

Prokaryotic condensins[edit]

Prokaryotic species also have condensin-like complexes that play an important role in chromosome organization and segregation. The prokaryotic condensins can be classified into two types: SMC-ScpAB[11] and MukBEF.[12] Many eubacterial and archaeal species have SMC-ScpAB, whereas a subgroup of eubacteria (known as gamma-proteobacteria) has MukBEF.

Complex Subunit Classification B. subtilis Caulobacter E.coli
SMC-ScpAB SMC ATPase SMC/BsSMC SMC -
SMC-ScpAB ScpA kleisin ScpA ScpA -
SMC-ScpAB ScpB  ? ScpB ScpB -
MukBEF MukB ATPase - - MukB
MukBEF MukE  ? - - MukE
MukBEF MukF kleisin - - MukF

Molecular mechanisms[edit]

Molecular activities[edit]

Purified condensin I introduces positive superhelical tension into double-stranded DNA in an ATP-hydrolysis-dependent manner.[13] It also displays a DNA-stimulated ATPase activity in vitro. An SMC2-SMC4 dimer has an ability to reanneal complementary single-stranded DNA.[14] This activity does not require ATP.

Molecular structures[edit]

SMC dimers that act as the core subunits of condensins display a highly unique V-shape (see SMC proteins for details).[15] The holocomplex of condensin I has been visualized by electron microscopy.[16]

Mitotic functions[edit]

Distribution of condensin I (green) and condensin II (red) in human metaphase chromosomes. Bar, 1 μm.

In human tissue culture cells, the two condensin complexes are regulated differently during the cell cycle.[17][18] Condensin II is present within the cell nucleus during interphase and is involved in an early stage of chromosome condensation within the prophase nucleus. On the other hand, condensin I is present in the cytoplasm during interphase, and gains access to chromosomes only after the nuclear envelope breaks down at the end of prophase. During prometaphase and metaphase, both condensin I and condensin II contribute to the assembly of condensed chromosomes, in which two sister chromatids are fully resolved.[4] The two complexes apparently stay associated with chromosomes after the sister chromatids separate from each other in anaphase. At least one of the subunits of condensin I is known to be a direct target of a cyclin-dependent kinase (Cdk).[19]

Chromosomal functions outside of mitosis[edit]

Recent studies have shown that condensins participate in a wide variety of chromosome functions outside of mitosis or meiosis. In budding yeast, for instance, condensin I (the sole condensin in this organism) is involved in copy number regulation of the rDNA repeat[20] as well as in clustering of the tRNA genes.[21] In Drosophila, condensin II subunits contribute to the dissolution of polytene chromosomes[22] and the formation of chromosome territories[23] in ovarian nurse cells. Evidence is also available that they negatively regulate transvection in diploid cells. In A. thaliana, condensin II is essential for tolerance of excess boron stress, possibly by alleviating DNA damage.[24] It has been shown that, in human cells, condensin II’s contribution to resolving sister chromatids initiates as early as in S phase.[25]

Relatives[edit]

Eukaryotic cells have two additional classes of SMC protein complexes. Cohesin contains SMC1 and SMC3 and is involved in sister chromatid cohesion. The SMC5/6 complex contains SMC5 and SMC6 and is implicated in recombinational repair.

See also[edit]

References[edit]

  1. ^ Hirano T (2012). "Condensins: universal organizers of chromosomes with diverse functions". Genes Dev 26 (15): 1659–1678. doi:10.1101/gad.194746.112. PMID 22855829. 
  2. ^ Wood AJ, Severson, AF, Meyer BJ (2010). "Condensin and cohesin complexity: the expanding repertoire of functions". Nat Rev Genet 11 (6): 391–404. doi:10.1038/nrg2794. PMID 20442714. 
  3. ^ Hirano T, Kobayashi R, Hirano M. (1997). "Condensins, chromosome condensation complex containing XCAP-C, XCAP-E and a Xenopus homolog of the Drosophila Barren protein". Cell 89 (4): 511–21. doi:10.1016/S0092-8674(00)80233-0. PMID 9160743. 
  4. ^ a b Ono T, Losada A, Hirano M, Myers MP, Neuwald AF, Hirano T. (2003). "Differential contributions of condensin I and condensin II to mitotic chromosome architecture in vertebrate cells". Cell 115 (1): 109–21. doi:10.1016/S0092-8674(03)00724-4. PMID 14532007. 
  5. ^ Schleiffer A, Kaitna S, Maurer-Stroh S, Glotzer M, Nasmyth K, Eisenhaber F. (2003). "Kleisins: a superfamily of bacterial and eukaryotic SMC protein partners". Mol. Cell 11 (3): 571–5. doi:10.1016/S1097-2765(03)00108-4. PMID 12667442. 
  6. ^ Neuwald AF, Hirano T. (2000). "HEAT repeats associated with condensins, cohesins, and other complexes involved in chromosome-related functions". Genome Res. 10 (10): 1445–52. doi:10.1101/gr.147400. PMID 11042144. 
  7. ^ 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. doi:10.1016/j.cub.2008.12.006. PMID 19119011. 
  8. ^ Sutani T, Yuasa T, Tomonaga T, Dohmae N, Takio K, Yanagida M. (1999). "Fission yeast condensin complex: essential roles of non-SMC subunits for condensation and Cdc2 phosphorylation of Cut3/SMC4". Genes Dev. 13 (17): 2271–83. doi:10.1101/gad.13.17.2271. PMID 10485849. 
  9. ^ Freeman L, Aragon-Alcaide L, Strunnikov A. (2000). "The condensin complex governs chromosome condensation and mitotic transmission of rDNA". J. Cell Biol. 149 (4): 811–824. doi:10.1083/jcb.149.4.811. PMID 10811823. 
  10. ^ Fujiwara T, Tanaka K, Kuroiwa T, Hirano T. (2013). "Spatiotemporal dynamics of condensins I and II: evolutionary insights from the primitive red alga Cyanidioschyzon merolae". Mol. Biol. Cell. 24 (16): 2515–27. doi:10.1091/mbc.E13-04-0208. PMID 23783031. 
  11. ^ Mascarenhas J, Soppa J, Strunnikov AV, Graumann PL. (2002). "Cell cycle-dependent localization of two novel prokaryotic chromosome segregation and condensation proteins in Bacillus subtilis that interact with SMC protein". EMBO J. 21 (12): 3108–18. doi:10.1093/emboj/cdf314. PMID 12065423. 
  12. ^ Yamazoe M, Onogi T, Sunako Y, Niki H, Yamanaka K, Ichimura T, Hiraga S. (1999). "Complex formation of MukB, MukE and MukF proteins involved in chromosome partitioning in Escherichia coli". EMBO J. 18 (21): 5873–84. doi:10.1093/emboj/18.21.5873. PMID 10545099. 
  13. ^ Kimura K, Hirano T. (1997). "ATP-dependent positive supercoiling of DNA by 13S condensin: a biochemical implication for chromosome condensation". Cell 90 (4): 625–634. doi:10.1016/s0092-8674(00)80524-3. PMID 9288743. 
  14. ^ Sutani T, Yanagida M. (1997). "DNA renaturation activity of the SMC complex implicated in chromosome condensation". Nature 388 (6644): 798–801. doi:10.1038/42062. PMID 9285594. 
  15. ^ Melby TE, Ciampaglio CN, Briscoe G, Erickson HP. (1998). "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. doi:10.1083/jcb.142.6.1595. PMID 9744887. 
  16. ^ Anderson DE, Losada A, Erickson HP, Hirano T. (2002). "Condensin and cohesin display different arm conformations with characteristic hinge angles". J. Cell Biol. 156 (6): 419–424. doi:10.1083/jcb.200111002. PMID 11815634. 
  17. ^ Ono T, Fang Y, Spector DL, Hirano T (2004). "Spatial and temporal regulation of Condensins I and II in mitotic chromosome assembly in human cells". Mol. Biol. Cell 15 (7): 3296–308. doi:10.1091/mbc.E04-03-0242. PMID 15146063. 
  18. ^ Hirota T, Gerlich D, Koch B, Ellenberg J, Peters JM (2004). "Distinct functions of condensin I and II in mitotic chromosome assembly". J. Cell Sci. 117 (Pt 26): 6435–45. doi:10.1242/jcs.01604. PMID 15572404. 
  19. ^ Kimura K, Hirano M, Kobayashi R, Hirano T (1998). "Phosphorylation and activation of 13S condensin by Cdc2 in vitro". Science 282 (5388): 487–490. doi:10.1126/science.282.5388.487. PMID 9774278. 
  20. ^ Johzuka K, Terasawa M, Ogawa H, Ogawa T, Horiuchi T (2006). "Condensin loaded onto the replication fork barrier site in the rRNA gene repeats during S phase in a FOB1-dependent fashion to prevent contraction of a long repetitive array in Saccharomyces cerevisiae.". Mol Cell Biol. 26 (6): 2226–2236. doi:10.1128/MCB.26.6.2226-2236.2006. PMID 16507999. 
  21. ^ Haeusler RA, Pratt-Hyatt M, Good PD, Gipson TA, Engelke DR (2008). "Clustering of yeast tRNA genes is mediated by specific association of condensin with tRNA gene transcription complexes.". Genes Dev. 22 (16): 2204–2214. doi:10.1101/gad.1675908. PMID 18708579. 
  22. ^ Hartl TA, Smith HF, Bosco G (2008). "Chromosome alignment and transvection are antagonized by condensin II.". Science 322 (5906): 1384–1387. doi:10.1126/science.1164216. PMID 19039137. 
  23. ^ Bauer CR, Hartl TA, Bosco G. (2012). "Condensin II promotes the formation of chromosome territories by inducing axial compaction of polyploid interphase chromosomes.". PLoS Genet 8 (8): e1002873. doi:10.1371/journal.pgen.1002873. PMID 22956908. 
  24. ^ Sakamoto T, Inui YT, Uraguchi S, Yoshizumi T, Matsunaga S, Mastui M, Umeda M, Fukui K, Fujiwara T. (2011). "Condensin II alleviates DNA damage and is essential for tolerance of boron overload stress in Arabidopsis.". Plant cell 23 (9): 3533–3546. doi:10.1105/tpc.111.086314. PMID 21917552. 
  25. ^ Ono T, Yamashita D, Hirano T (2013). "Condensin II initiates sister chromatid resolution during S phase". J. Cell Biol. 200 (4): 429–441. doi:10.1083/jcb.201208008. PMID 23401001. 

External links[edit]