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  • Review Article
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Condensin and cohesin: more than chromosome compactor and glue

Nature Reviews Genetics volume 4, pages 520–534 (2003)Cite this article

Key Points

  • Although distinct in structure and function, cohesin and condensin both contain conserved chromosomal ATPases of the structural maintenance of chromosomes (SMC) protein family. Present models indicate that cohesin might encircle two sister chromatids to promote their cohesion, whereas condensin might stabilize supercoiled DNA loops on a single chromatid to promote its condensation. Whether the diversity of functions exhibited by each complex during interphase and mitosis reflects a common molecular mechanism remains unknown.

  • Cohesin and condensin affect gene expression through influences on control mechanisms that operate globally at a chromosome-wide level, regionally over a subchromosomal domain, or locally on an individual gene.

  • As well as a mitotic condensin complex, C. elegans contains a second condensin-like complex that mediates the global twofold repression of genes along hermaphrodite X chromosomes to achieve dosage compensation, a vital process that equalizes X-linked gene products between males (one X chromosome) and hermaphrodites (two X chromosomes). The complex also mediates the local 20-fold repression of a single autosomal gene.

  • A condensin subunit might help maintain repression over regulatory domains of the Drosophila body-patterning gene Abd-B.

  • Cohesin might need to be removed during mitosis to establish transcriptional silencing of the S. cerevisiae mating-type locus, whereas condensin might facilitate silencing over this domain.

  • In S. cerevisiae, cohesin localizes to several DNA segments that border regions of active and silent chromatin and might be required for their chromatin insulation function.

  • A cohesin regulatory protein might facilitate contact between a distant enhancer and the promoter of the Drosophila wing gene cut.

  • In several organisms, cohesin subunits associate with DNA-repair proteins to form new complexes with roles in DNA repair. Accordingly, mutations in several cohesin subunits show hypersensitivity to DNA damage.

  • Condensin and some cohesin subunits have been implicated in the DNA-damage checkpoint-signalling pathway.

  • Cohesin, and possibly condensin, might help organize the structure and orientation of the centromere, so that sister chromatids are properly captured by microtubules from opposite poles of the spindle. Mutations in cohesin subunits trigger the spindle checkpoint.

Abstract

Two related protein complexes, cohesin and condensin, are essential for separating identical copies of the genome into daughter cells during cell division. Cohesin glues replicated sister chromatids together until they split at anaphase, whereas condensin reorganizes chromosomes into their highly compact mitotic structure. Unexpectedly, mutations in the subunits of these complexes have been uncovered in genetic screens that target completely different processes. Exciting new evidence is emerging that cohesin and condensin influence crucial processes during interphase, and unforeseen aspects of mitosis. Each complex can perform several roles, and individual subunits can associate with different sets of proteins to achieve diverse functions, including the regulation of gene expression, DNA repair, cell-cycle checkpoints and centromere organization.

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Figure 1: A condensin-like complex mediates gene-specific and chromosome-wide repression in Caenorhabditis elegans.
Figure 2: Cohesin and condensin might influence silencing and insulation at the yeast mating-type locus.
Figure 3: Condensin might influence silencing or insulation at elements that regulate fly body-segment identity.
Figure 4: A cohesin regulatory protein might affect enhancer–promoter communication in Drosophila.
Figure 5: Cohesin subunits participate in a DNA-damage-checkpoint response pathway.
Figure 6: Cohesin and condensin at the centromere.

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References

  1. Cobbe, N. & Heck, M. M. SMCs in the world of chromosome biology — from prokaryotes to higher eukaryotes. J. Struct. Biol. 129, 123–143 (2000).

    CAS  PubMed  Google Scholar 

  2. Hirano, T. The ABCs of SMC proteins: two-armed ATPases for chromosome condensation, cohesion, and repair. Genes Dev. 16, 399–414 (2002).

    Article  CAS  PubMed  Google Scholar 

  3. Jessberger, R. The many functions of SMC proteins in chromosome dynamics. Nature Rev. Mol. Cell Biol. 3, 767–778 (2002).

    CAS  Google Scholar 

  4. Nasmyth, K. Disseminating the genome: joining, resolving, and separating sister chromatids during mitosis and meiosis. Annu. Rev. Genet. 35, 673–745 (2001).

    CAS  PubMed  Google Scholar 

  5. Lee, J. Y. & Orr-Weaver, T. L. The molecular basis of sister-chromatid cohesion. Annu. Rev. Cell Dev. Biol. 17, 753–777 (2001).

    CAS  PubMed  Google Scholar 

  6. Hirano, T. Chromosome cohesion, condensation, and separation. Annu. Rev. Biochem. 69, 115–144 (2000).

    CAS  PubMed  Google Scholar 

  7. Guacci, V., Koshland, D. & Strunnikov, A. A direct link between sister chromatid cohesion and chromosome condensation revealed through the analysis of MCD1 in S. cerevisiae. Cell 91, 47–57 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Michaelis, C., Ciosk, R. & Nasmyth, K. Cohesins: chromosomal proteins that prevent premature separation of sister chromatids. Cell 91, 35–45 (1997). References 7 and 8 describe the initial genetic screens that identified subunits of cohesin and provided the first description of their function.

    CAS  PubMed  Google Scholar 

  9. Toth, A. et al. Yeast cohesin complex requires a conserved protein, Eco1p(Ctf7), to establish cohesion between sister chromatids during DNA replication. Genes Dev. 13, 320–333 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Tomonaga, T. et al. Characterization of fission yeast cohesin: essential anaphase proteolysis of Rad21 phosphorylated in the S phase. Genes Dev. 14, 2757–2770 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Uhlmann, F., Lottspeich, F. & Nasmyth, K. Sister-chromatid separation at anaphase onset is promoted by cleavage of the cohesin subunit Scc1. Nature 400, 37–42 (1999). This paper identifies the cohesin subunit that is proteolytically cleaved at anaphase and provides a mechanistic explanation for the release of cohesion and separation of sister chromatids.

    CAS  PubMed  Google Scholar 

  12. Hauf, S., Waizenegger, I. C. & Peters, J. M. Cohesin cleavage by separase required for anaphase and cytokinesis in human cells. Science 293, 1320–1323 (2001).

    CAS  PubMed  Google Scholar 

  13. Rogers, E., Bishop, J. D., Waddle, J. A., Schumacher, J. M. & Lin, R. The aurora kinase AIR-2 functions in the release of chromosome cohesion in Caenorhabditis elegans meiosis. J. Cell Biol. 157, 219–229 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Saka, Y. et al. Fission yeast cut3 and cut14, members of a ubiquitous protein family, are required for chromosome condensation and segregation in mitosis. EMBO J. 13, 4938–4952 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Hirano, T. & Mitchison, T. J. A heterodimeric coiled-coil protein required for mitotic chromosome condensation in vitro. Cell 79, 449–458 (1994).

    CAS  PubMed  Google Scholar 

  16. Hirano, T., Kobayashi, R. & Hirano, M. Condensins, chromosome condensation protein complexes containing XCAP-C, XCAP-E and a Xenopus homolog of the Drosophila Barren protein. Cell 89, 511–521 (1997). References 15 and 16 show that SMC proteins are required for chromosome condensation and the biochemical identification of the condensin complex.

    CAS  PubMed  Google Scholar 

  17. Strunnikov, A. V., Hogan, E. & Koshland, D. SMC2, a Saccharomyces cerevisiae gene essential for chromosome segregation and condensation, defines a subgroup within the SMC family. Genes Dev. 9, 587–599 (1995).

    CAS  PubMed  Google Scholar 

  18. Freeman, L., Aragon-Alcaide, L. & Strunnikov, A. The condensin complex governs chromosome condensation and mitotic transmission of rDNA. J. Cell Biol. 149, 811–824 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Lavoie, B. D., Tuffo, K. M., Oh, S., Koshland, D. & Holm, C. Mitotic chromosome condensation requires Brn1p, the yeast homologue of Barren. Mol. Biol. Cell 11, 1293–1304 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Ouspenski, I. I., Cabello, O. A. & Brinkley, B. R. Chromosome condensation factor Brn1p is required for chromatid separation in mitosis. Mol. Biol. Cell 11, 1305–1313 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Steffensen, S. et al. A role for Drosophila SMC4 in the resolution of sister chromatids in mitosis. Curr. Biol. 11, 295–307 (2001).

    CAS  PubMed  Google Scholar 

  22. Hagstrom, K. A., Holmes, V. F., Cozzarelli, N. R. & Meyer, B. J. C. elegans condensin promotes mitotic chromosome architecture, centromere organization, and sister chromatid segregation during mitosis and meiosis. Genes Dev. 16, 729–742 (2002). Along with reference 80, this paper indicates that condensin subunit homologues in C. elegans might localize to the centromere and have a role in building and orientating the centromere towards the spindle poles during chromosome condensation. It also shows that in mitosis, MIX-1 associates with an SMC homologue that is not involved in dosage compensation.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Bhat, M. A., Philp, A. V., Glover, D. M. & Bellen, H. J. Chromatid segregation at anaphase requires the barren product, a novel chromosome-associated protein that interacts with Topoisomerase II. Cell 87, 1103–1114 (1996).

    PubMed  Google Scholar 

  24. Sutani, T. et al. Fission yeast condensin complex: essential roles of non-SMC subunits for condensation and Cdc2 phosphorylation of Cut3/SMC4. Genes Dev. 13, 2271–2283 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Meyer, B. J. Sex in the worm: counting and compensating X-chromosome dose. Trends Genet. 16, 247–253 (2000).

    CAS  PubMed  Google Scholar 

  26. Lieb, J. D., Albrecht, M. R., Chuang, P. T. & Meyer, B. J. MIX-1: an essential component of the C. elegans mitotic machinery executes X chromosome dosage compensation. Cell 92, 265–277 (1998).

    CAS  PubMed  Google Scholar 

  27. Chuang, P. T., Albertson, D. G. & Meyer, B. J. DPY-27: a chromosome condensation protein homolog that regulates C. elegans dosage compensation through association with the X chromosome. Cell 79, 459–474 (1994). In the search for proteins that mediate the repression of X-linked genes during C. elegans dosage compensation (references 26 and 27), homologues of condensin SMC subunits were identified. This established the first connection between condensin and gene regulation.

    CAS  PubMed  Google Scholar 

  28. Lieb, J. D., Capowski, E. E., Meneely, P. & Meyer, B. J. DPY-26, a link between dosage compensation and meiotic chromosome segregation in the nematode. Science 274, 1732–1736 (1996).

    CAS  PubMed  Google Scholar 

  29. Albrecht, M. R. Analysis of dosage compensation and chromosome segregation in Caenorhabditis elegans. Thesis, Univ. California, Berkeley (1998).

  30. Hodgkin, J. X chromosome dosage and gene expression in Caenorhabditis elegans: two unusual dumpy genes. Mol. Gen. Genet. 192, 452–458 (1983).

    Google Scholar 

  31. Plenefisch, J. D., DeLong, L. & Meyer, B. J. Genes that implement the hermaphrodite mode of dosage compensation in Caenorhabditis elegans. Genetics 121, 57–76 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Chu, D. S. et al. A molecular link between gene-specific and chromosome-wide transcriptional repression. Genes Dev. 16, 796–805 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Martinez-Balbas, M. A., Dey, A., Rabindran, S. K., Ozato, K. & Wu, C. Displacement of sequence-specific transcription factors from mitotic chromatin. Cell 83, 29–38 (1995).

    CAS  PubMed  Google Scholar 

  34. West, A. G., Gaszner, M. & Felsenfeld, G. Insulators: many functions, many mechanisms. Genes Dev. 16, 271–288 (2002).

    PubMed  Google Scholar 

  35. Bi, X. & Broach, J. R. Chromosomal boundaries in S. cerevisiae. Curr. Opin. Genet. Dev. 11, 199–204 (2001).

    CAS  PubMed  Google Scholar 

  36. Li, Y. C., Cheng, T. H. & Gartenberg, M. R. Establishment of transcriptional silencing in the absence of DNA replication. Science 291, 650–653 (2001).

    CAS  PubMed  Google Scholar 

  37. Kirchmaier, A. L. & Rine, J. DNA replication-independent silencing in S. cerevisiae. Science 291, 646–650 (2001).

    CAS  PubMed  Google Scholar 

  38. Lau, A., Blitzblau, H. & Bell, S. P. Cell-cycle control of the establishment of mating-type silencing in S. cerevisiae. Genes Dev. 16, 2935–2945 (2002). References 38, 43, 44, 50 and 51 provide intriguing suggestions for new roles of cohesin or condensin subunits in aspects of gene regulation, including silencing, chromatin insulator function and enhancer–promoter communication.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Laloraya, S., Guacci, V. & Koshland, D. Chromosomal addresses of the cohesin component Mcd1p. J. Cell Biol. 151, 1047–1056 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Nonaka, N. et al. Recruitment of cohesin to heterochromatic regions by Swi6/HP1 in fission yeast. Nature Cell Biol. 4, 89–93 (2002).

    CAS  PubMed  Google Scholar 

  41. Bernard, P. et al. Requirement of heterochromatin for cohesion at centromeres. Science 294, 2539–2542 (2001). References 40 and 41 show that fission yeast centromeric heterochromatin proteins are required for recruiting cohesin to the centromere and for sister-chromatid cohesion at centromeres but not chromosome arms.

    CAS  PubMed  Google Scholar 

  42. Blat, Y. & Kleckner, N. Cohesins bind to preferential sites along yeast chromosome III, with differential regulation along arms versus the centric region. Cell 98, 249–259 (1999).

    CAS  PubMed  Google Scholar 

  43. Donze, D., Adams, C. R., Rine, J. & Kamakaka, R. T. The boundaries of the silenced HMR domain in Saccharomyces cerevisiae. Genes Dev. 13, 698–708 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Bhalla, N., Biggins, S. & Murray, A. W. Mutation of YCS4, a budding yeast condensin subunit, affects mitotic and nonmitotic chromosome behavior. Mol. Biol. Cell 13, 632–645 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Simon, J. A. & Tamkun, J. W. Programming off and on states in chromatin: mechanisms of Polycomb and trithorax group complexes. Curr. Opin. Genet. Dev. 12, 210–218 (2002).

    CAS  PubMed  Google Scholar 

  46. Gyurkovics, H., Gausz, J., Kummer, J. & Karch, F. A new homeotic mutation in the Drosophila bithorax complex removes a boundary separating two domains of regulation. EMBO J. 9, 2579–2585 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Hagstrom, K., Muller, M. & Schedl, P. Fab-7 functions as a chromatin domain boundary to ensure proper segment specification by the Drosophila bithorax complex. Genes Dev. 10, 3202–3215 (1996).

    CAS  PubMed  Google Scholar 

  48. Zhou, J., Barolo, S., Szymanski, P. & Levine, M. The Fab-7 element of the bithorax complex attenuates enhancer–promoter interactions in the Drosophila embryo. Genes Dev. 10, 3195–3201 (1996).

    CAS  PubMed  Google Scholar 

  49. Mihaly, J., Hogga, I., Gausz, J., Gyurkovics, H. & Karch, F. In situ dissection of the Fab-7 region of the bithorax complex into a chromatin domain boundary and a Polycomb-response element. Development 124, 1809–1820 (1997).

    CAS  PubMed  Google Scholar 

  50. Lupo, R., Breiling, A., Bianchi, M. E. & Orlando, V. Drosophila chromosome condensation proteins Topoisomerase II and Barren colocalize with Polycomb and maintain Fab-7 PRE silencing. Mol. Cell 7, 127–136 (2001).

    CAS  PubMed  Google Scholar 

  51. Rollins, R. A., Morcillo, P. & Dorsett, D. Nipped-B, a Drosophila homologue of chromosomal adherins, participates in activation by remote enhancers in the cut and Ultrabithorax genes. Genetics 152, 577–593 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Lehmann, A. R. et al. The rad18 gene of Schizosaccharomyces pombe defines a new subgroup of the SMC superfamily involved in DNA repair. Mol. Cell Biol. 15, 7067–7080 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Fousteri, M. I. & Lehmann, A. R. A novel SMC protein complex in Schizosaccharomyces pombe contains the Rad18 DNA repair protein. EMBO J. 19, 1691–1702 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 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. 277, 21585–21591 (2002).

    CAS  PubMed  Google Scholar 

  55. Nasim, A. & Smith, B. P. Genetic control of radiation sensitivity in Schizosaccharomyces pombe. Genetics 79, 573–582 (1975).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Verkade, H. M., Bugg, S. J., Lindsay, H. D., Carr, A. M. & O'Connell, M. J. Rad18 is required for DNA repair and checkpoint responses in fission yeast. Mol. Biol. Cell 10, 2905–2918 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Jessberger, R., Riwar, B., Baechtold, H. & Akhmedov, A. T. SMC proteins constitute two subunits of the mammalian recombination complex RC-1. EMBO J. 15, 4061–4068 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Birkenbihl, R. P. & Subramani, S. Cloning and characterization of rad21 an essential gene of Schizosaccharomyces pombe involved in DNA double-strand-break repair. Nucleic Acids Res. 20, 6605–6611 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Sonoda, E. et al. Scc1/Rad21/Mcd1 is required for sister chromatid cohesion and kinetochore function in vertebrate cells. Dev. Cell 1, 759–770 (2001).

    CAS  PubMed  Google Scholar 

  60. Sjogren, C. & Nasmyth, K. Sister chromatid cohesion is required for postreplicative double-strand break repair in Saccharomyces cerevisiae. Curr. Biol. 11, 991–995 (2001).

    CAS  PubMed  Google Scholar 

  61. Yazdi, P. T. et al. SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint. Genes Dev. 16, 571–582 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Kim, S. T., Xu, B. & Kastan, M. B. Involvement of the cohesin protein, Smc1, in Atm-dependent and independent responses to DNA damage. Genes Dev. 16, 560–570 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Aono, N., Sutani, T., Tomonaga, T., Mochida, S. & Yanagida, M. Cnd2 has dual roles in mitotic condensation and interphase. Nature 417, 197–202 (2002). References 61–63 provide evidence that cohesin and condensin subunits are involved in DNA repair and the DNA-damage checkpoint.

    CAS  PubMed  Google Scholar 

  64. Tanaka, T., Cosma, M. P., Wirth, K. & Nasmyth, K. Identification of cohesin association sites at centromeres and along chromosome arms. Cell 98, 847–858 (1999).

    CAS  PubMed  Google Scholar 

  65. Van Hooser, A. A. et al. Specification of kinetochore-forming chromatin by the histone H3 variant CENP-A. J. Cell Sci. 114, 3529–3542 (2001).

    CAS  PubMed  Google Scholar 

  66. Berger, S. L. Molecular biology: the histone modification circus. Science 292, 64–65 (2001).

    CAS  PubMed  Google Scholar 

  67. Toyoda, Y. et al. Requirement of chromatid cohesion proteins rad21/scc1 and mis4/scc2 for normal spindle-kinetochore interaction in fission yeast. Curr. Biol. 12, 347–358 (2002).

    CAS  PubMed  Google Scholar 

  68. Zheng, L., Chen, Y. & Lee, W. H. Hec1p, an evolutionarily conserved coiled-coil protein, modulates chromosome segregation through interaction with SMC proteins. Mol. Cell Biol. 19, 5417–5428 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Tanaka, T., Fuchs, J., Loidl, J. & Nasmyth, K. Cohesin ensures bipolar attachment of microtubules to sister centromeres and resists their precocious separation. Nature Cell Biol. 2, 492–499 (2000). Along with references 59 and 70, this shows that cohesin is required for the bi-polar attachment of sister chromatids to microtubules from opposite poles. Accordingly, reference 67 finds that mutations in cohesin subunits trigger the spindle checkpoint.

    CAS  PubMed  Google Scholar 

  70. He, X., Asthana, S. & Sorger, P. K. Transient sister chromatid separation and elastic deformation of chromosomes during mitosis in budding yeast. Cell 101, 763–775 (2000).

    CAS  PubMed  Google Scholar 

  71. Janke, C., Ortiz, J., Tanaka, T. U., Lechner, J. & Schiebel, E. Four new subunits of the Dam1–Duo1 complex reveal novel functions in sister kinetochore biorientation. EMBO J. 21, 181–193 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Tanaka, T. U. et al. Evidence that the Ipl1–Sli15 (Aurora kinase–INCENP) complex promotes chromosome bi-orientation by altering kinetochore–spindle pole connections. Cell 108, 317–329 (2002).

    CAS  PubMed  Google Scholar 

  73. Biggins, S. & Murray, A. W. The budding yeast protein kinase Ipl1/Aurora allows the absence of tension to activate the spindle checkpoint. Genes Dev. 15, 3118–3129 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Morishita, J. et al. Bir1/Cut17 moving from chromosome to spindle upon the loss of cohesion is required for condensation, spindle elongation and repair. Genes Cells 6, 743–763 (2001).

    CAS  PubMed  Google Scholar 

  75. Vass, S. et al. Depletion of drad21/scc1 in Drosophila cells leads to instability of the cohesin complex and disruption of mitotic progression. Curr. Biol. 13, 208–218 (2003).

    CAS  PubMed  Google Scholar 

  76. Millband, D. N., Campbell, L. & Hardwick, K. G. The awesome power of multiple model systems: interpreting the complex nature of spindle checkpoint signaling. Trends Cell Biol. 12, 205–209 (2002).

    CAS  PubMed  Google Scholar 

  77. Gregson, H. C. et al. A potential role for human cohesin in mitotic spindle aster assembly. J. Biol. Chem. 276, 47575–47582 (2001).

    CAS  PubMed  Google Scholar 

  78. Skibbens, R. V., Corson, L. B., Koshland, D. & Hieter, P. Ctf7p is essential for sister chromatid cohesion and links mitotic chromosome structure to the DNA replication machinery. Genes Dev. 13, 307–319 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Hanna, J. S., Kroll, E. S., Lundblad, V. & Spencer, F. A. Saccharomyces cerevisiae CTF18 and CTF4 are required for sister chromatid cohesion. Mol. Cell Biol. 21, 3144–3158 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Stear, J. H. & Roth, M. B. Characterization of HCP-6, a C. elegans protein required to prevent chromosome twisting and merotelic attachment. Genes Dev. 16, 1498–1508 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Wignall, S. M., Deehan, R., Maresca, T. J. & Heald, R. The condensin complex is required for proper spindle assembly and chromosome segregation in Xenopus egg extracts. J. Cell Biol. (in the press).

  82. Lavoie, B. D., Hogan, E. & Koshland, D. In vivo dissection of the chromosome condensation machinery: reversibility of condensation distinguishes contributions of condensin and cohesin. J. Cell Biol. 156, 805–815 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Peters, J. M. The anaphase-promoting complex: proteolysis in mitosis and beyond. Mol. Cell 9, 931–943 (2002).

    CAS  PubMed  Google Scholar 

  84. Nasmyth, K. Segregating sister genomes: the molecular biology of chromosome separation. Science 297, 559–565 (2002).

    CAS  PubMed  Google Scholar 

  85. Losada, A., Hirano, M. & Hirano, T. Identification of Xenopus SMC protein complexes required for sister chromatid cohesion. Genes Dev. 12, 1986–1997 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Losada, A., Yokochi, T., Kobayashi, R. & Hirano, T. Identification and characterization of SA/Scc3p subunits in the Xenopus and human cohesin complexes. J. Cell Biol. 150, 405–416 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Sumara, I., Vorlaufer, E., Gieffers, C., Peters, B. H. & Peters, J. M. Characterization of vertebrate cohesin complexes and their regulation in prophase. J. Cell Biol. 151, 749–762 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Chan, R. C. et al. Chromosome cohesion is regulated by C. elegans TIM-1, a paralog of the clock protein TIMELESS. Nature (in the press).

  89. Uhlmann, F. & Nasmyth, K. Cohesion between sister chromatids must be established during DNA replication. Curr. Biol. 8, 1095–1101 (1998).

    CAS  PubMed  Google Scholar 

  90. Watanabe, Y., Yokobayashi, S., Yamamoto, M. & Nurse, P. Pre-meiotic S phase is linked to reductional chromosome segregation and recombination. Nature 409, 359–363 (2001).

    CAS  PubMed  Google Scholar 

  91. Waizenegger, I. C., Hauf, S., Meinke, A. & Peters, J. M. Two distinct pathways remove mammalian cohesin from chromosome arms in prophase and from centromeres in anaphase. Cell 103, 399–410 (2000).

    CAS  PubMed  Google Scholar 

  92. Losada, A., Hirano, M. & Hirano, T. Cohesin release is required for sister chromatid resolution, but not for condensin-mediated compaction, at the onset of mitosis. Genes Dev. 16, 3004–3016 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Megee, P. C. & Koshland, D. A functional assay for centromere-associated sister chromatid cohesion. Science 285, 254–257 (1999).

    CAS  PubMed  Google Scholar 

  94. Losada, A. & Hirano, T. Biology in pictures: new light on sticky sisters. Curr. Biol. 10, 615 (2000).

    Google Scholar 

  95. Klein, F. et al. A central role for cohesins in sister chromatid cohesion, formation of axial elements, and recombination during yeast meiosis. Cell 98, 91–103 (1999).

    CAS  PubMed  Google Scholar 

  96. Buonomo, S. B. et al. Disjunction of homologous chromosomes in meiosis I depends on proteolytic cleavage of the meiotic cohesin Rec8 by separin. Cell 103, 387–398 (2000).

    CAS  PubMed  Google Scholar 

  97. Pasierbek, P. et al. A Caenorhabditis elegans cohesion protein with functions in meiotic chromosome pairing and disjunction. Genes Dev. 15, 1349–1360 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Uhlmann, F., Wernic, D., Poupart, M. A., Koonin, E. V. & Nasmyth, K. Cleavage of cohesin by the CD clan protease separin triggers anaphase in yeast. Cell 103, 375–386 (2000).

    CAS  PubMed  Google Scholar 

  99. Kimura, K., Rybenkov, V. V., Crisona, N. J., Hirano, T. & Cozzarelli, N. R. 13S condensin actively reconfigures DNA by introducing global positive writhe: implications for chromosome condensation. Cell 98, 239–248 (1999).

    CAS  PubMed  Google Scholar 

  100. Kimura, K., Cuvier, O. & Hirano, T. Chromosome condensation by a human condensin complex in Xenopus egg extracts. J. Biol. Chem. 276, 5417–5420 (2001).

    CAS  PubMed  Google Scholar 

  101. Losada, A. & Hirano, T. Intermolecular DNA interactions stimulated by the cohesin complex in vitro: implications for sister chromatid cohesion. Curr. Biol. 11, 268–272 (2001).

    CAS  PubMed  Google Scholar 

  102. Anderson, D. E., Losada, A., Erickson, H. P. & Hirano, T. Condensin and cohesin display different arm conformations with characteristic hinge angles. J. Cell Biol. 156, 419–424 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Yoshimura, S. H. et al. Condensin architecture and interaction with DNA: regulatory non-SMC subunits bind to the head of SMC heterodimer. Curr. Biol. 12, 508–513 (2002).

    CAS  PubMed  Google Scholar 

  104. Bazett-Jones, D. P., Kimura, K. & Hirano, T. Efficient supercoiling of DNA by a single condensin complex as revealed by electron spectroscopic imaging. Mol. Cell 9, 1183–1190 (2002).

    CAS  PubMed  Google Scholar 

  105. Swedlow, J. R. & Hirano, T. The making of the mitotic chromosome: modern insights into classical questions. Mol. Cell 11, 557–569 (2003).

    CAS  PubMed  Google Scholar 

  106. Haering, C. H., Lowe, J., Hochwagen, A. & Nasmyth, K. Molecular architecture of SMC proteins and the yeast cohesin complex. Mol. Cell 9, 773–788 (2002). References 102, 103 and 105 probe the molecular mechanisms of condensin and cohesin action. A common feature might be the ability to use the coiled-coil arms of the SMC proteins to enclose two DNA segments, either from the same sister chromatid (condensin) or from different sister chromatids (cohesin).

    CAS  PubMed  Google Scholar 

  107. Saitoh, N., Goldberg, I. G., Wood, E. R. & Earnshaw, W. C. 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, 303–318 (1994).

    CAS  PubMed  Google Scholar 

  108. Cubizolles, F. et al. pEg7, a new Xenopus protein required for mitotic chromosome condensation in egg extracts. J. Cell Biol. 143, 1437–1446 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Kaitna, S., Pasierbek, P., Jantsch, M., Loidl, J. & Glotzer, M. The aurora B kinase AIR-2 regulates kinetochores during mitosis and is required for separation of homologous chromosomes during meiosis. Curr. Biol. 12, 798–812 (2002).

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank R. Heald, S. Wignall, N. Bhalla and A. Severson for critical reading of the manuscript.

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Authors and Affiliations

  1. Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, 94720-3204, California, USA

    Kirsten A. Hagstrom & Barbara J. Meyer

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  1. Kirsten A. Hagstrom
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DATABASES

FlyBase

Abd-B

barr

cut

Fab-7

gluon

gypsy

Nipped-B

GeneDB

cnd2

cut3

cut14

mis4

rad18

rad21

OMIM

ataxia-telangiectasia

Bloom syndrome

Saccharomyces Genome Database

MCD1

PDS5

SCC3

SMC1

SMC2

SMC3

SMC4

YCS4

WormBase

dpy-26

dpy-27

dpy-28

her-1

mix-1

smc-4

xol-1

FURTHER INFORMATION

Chromatin Structure and Function page

Chromosome Passenger homepage

Mitosis World

Nature Cell Division web sites

Glossary

UBIQUITYLATION

The covalent addition of the small protein ubiquitin to another protein. Ubiquitin conjugation generally targets proteins for degradation by proteases.

PARALOGUES

Homologous genes in the same organism that have evolved from a gene duplication and a subsequent divergence of function.

POSITIVE SUPERCOILING

Twisting of the DNA about its own axis. Twisting opposite to the direction of the double-helix turns produces negative supercoils, whereas twisting in the same direction produces positive supercoils.

ATOMIC-FORCE MICROSCOPY

A method that maps submicroscopic surfaces to give information about their nature at the atomic level. A mechanical probe with a sharp tip is tracked over the surface of interest, and the deflection of the cantilevered tip is measured.

GENE CONVERSION

A specific type of recombination, which results in non-reciprocal genetic exchange, in which the sequence of one DNA strand is used to alter the sequence of the other.

PARASEGMENT

In Drosophila development, body-patterning genes are expressed in parasegmental units that are out of register with morphologically visible segments. A parasegment contains the posterior portion of one segment and the anterior section of the next segment.

TOPOISOMERASE II

An ATP-dependent enzyme that creates transient breaks in both strands of the DNA sugar-phosphate backbone, then passes one strand through the other and reseals the break. Such enzymes can remove or create supercoils in duplex DNA.

SYNTHETIC LETHALITY

A phenomenon that refers to lethality that is caused by the combination of two mutations, neither of which causes lethality by itself. Synthetic lethality of double mutants can indicate that two genes might function in related processes.

DNA LIGASE III

Ligases are enzymes that seal nicks in one strand of double-stranded DNA by creating an ester bond between adjacent 3′OH and 5′PO4 ends on the same strand. DNA ligase III acts in DNA repair to heal single-stranded DNA breaks.

DNA POLYMERASE-ε

Polymerases are enzymes that synthesize new DNA strands using a DNA template. DNA polymerase-ε acts in DNA repair when nucleotides have been excised, and also associates with the replication fork as a lagging-strand polymerase.

THYMINE DIMERS

A pair of abnormal covalently bonded adjacent thymine residues in DNA that are caused by DNA damage.

SPINDLE MIDZONE

A region of overlapping microtubules at the centre of the spindle-microtubule apparatus. The midzone forms when chromosomes segregate, and is required for proper spindle bi-polarity and elongation, chromosome movement and cytokinesis.

SPINDLE ASTER

A star-shaped cluster of microtubules that emanate towards the cell cortex from the microtubule-organizing centres at the poles of the spindle. Astral microtubules help position the mitotic apparatus.

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Hagstrom, K., Meyer, B. Condensin and cohesin: more than chromosome compactor and glue. Nat Rev Genet 4, 520–534 (2003). https://doi.org/10.1038/nrg1110

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