Condensin and cohesin: More than chromosome compactor and glue

Nature Reviews Genetics

Volumn 4, Issue 7, 2003, Pages 520-534

  Hagstrom, Kirsten A ^a   Meyer, Barbara J ^a  

^a University of California Berkeley   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COHESIN; CONDENSIN; DNA; GLUE PROTEIN; PROTEIN; UNCLASSIFIED DRUG;

CELL CYCLE; CELL DIVISION; CENTROMERE; CHROMOSOME; DNA REPAIR; GENE EXPRESSION REGULATION; GENOME; HUMAN; MITOSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN FUNCTION; REVIEW; SISTER CHROMATID;

ADENOSINE TRIPHOSPHATASES; ANIMALS; CELL CYCLE PROTEINS; CHROMATIN; CHROMOSOMAL PROTEINS, NON-HISTONE; DNA REPLICATION; DNA-BINDING PROTEINS; FUNGAL PROTEINS; HUMANS; MULTIPROTEIN COMPLEXES; NUCLEAR PROTEINS; SACCHAROMYCES CEREVISIAE;

EID: 0038141196     PISSN: 14710056     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrg1110     Document Type: Review

References (109)

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).
2. Hirano, T. The ABCs of SMC proteins: two-armed ATPases for chromosome condensation, cohesion, and repair. Genes Dev. 16, 399-414 (2002).
3. Jessberger, R. The many functions of SMC proteins in chromosome dynamics. Nature Rev Mol. Cell Biol. 3, 767-778 (2002).
4. Nasmyth, K. Disseminating the genome: joining, resolving, and separating sister chromatids during mitosis and meiosis. Annu. Rev. Genet. 35, 673-745 (2001).
5. Lee, J. Y. & Orr-Weaver, T. L. The molecular basis of sister-chromatid cohesion. Annu. Rev. Cell Dev. Biol. 17, 753-777 (2001).
6. Hirano, T. Chromosome cohesion, condensation, and separation. Annu. Rev. Biochem. 69, 115-144 (2000).
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).
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.
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).
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).
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.
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).
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).
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).
15. Hirano, T. & Mitchison, T. J. A heterodimeric coiled-coil protein required for mitotic chromosome condensation in vitro. Cell 79, 449-458 (1994).
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.
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).
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).
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).
20. Ouspenski, I. I., Cabello, O. A. & Brinkley, B. R. Chromosome condensation factor Bm1p is required for chromatid separation in mitosis. Mol. Biol. Cell 11, 1305-1313 (2000).
21. Steffensen, S. et al. A role for Drosophila SMC4 in the resolution of sister chromatids in mitosis. Curr. Biol. 11, 295-307 (2001).
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.
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).
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).
25. Meyer, B. J. Sex in the worm: counting and compensating X-chromosome dose. Trends Genet. 16, 247-253 (2000).
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).
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.
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).
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).
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).
32. Chu, D. S. et al. A molecular link between gene-specific and chromosome-wide transcriptional repression. Genes Dev. 16, 796-805 (2002).
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).
34. West, A. G., Gaszner, M. & Felsenfeld, G. Insulators: many functions, many mechanisms. Genes Dev. 16, 271-288 (2002).
35. Bi, X. & Broach, J. R. Chromosomal boundaries in S. cerevisiae. Curr. Opin. Genet. Dev. 11, 199-204 (2001).
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).
37. Kirchmaier, A. L. & Rine, J. DNA replication-independent silencing in S. cerevisiae. Science 291, 646-650 (2001).
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.
39. Laloraya, S., Guacci, V. & Koshland, D. Chromosomal addresses of the cohesin component Mcd1p. J. Cell Biol. 151, 1047-1056 (2000).
40. Nonaka, N. et al. Recruitment of cohesin to heterochromatic regions by Swi6/HP1 in fission yeast. Nature Cell Biol. 4, 89-93 (2002).
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.
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
55. Nasim, A. & Smith, B. P. Genetic control of radiation sensitivity in Schizosaccharomyces pombe. Genetics 79, 573-582 (1975).
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).
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).
58. Birkenbihi, 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).
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).
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).
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).
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).
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.
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).
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).
66. Berger, S. L. Molecular biology: the histone modification circus. Science 292, 64-65 (2001).
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).
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).
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.
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).
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).
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).
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).
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).
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).
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).
77. Gregson, H. C. et al. A potential role for human cohesin in mitotic spindle aster assembly. J. Biol. Chem. 276, 47575-47582 (2001).
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).
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).
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).
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).
83. Peters, J. M. The anaphase-promoting complex: proteolysis in mitosis and beyond. Mol. Cell 9, 931-943 (2002).
84. Nasmyth, K. Segregating sister genomes: the molecular biology of chromosome separation. Science 297, 559-565 (2002).
85. Losada, A., Hirano, M. & Hirano, T. Identification of Xenopus SMC protein complexes required for sister chromatid cohesion. Genes Dev. 12, 1986-1997 (1998).
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).
87. Sumara, J., 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).
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).
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).
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).
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).
93. Megee, P. C. & Koshland, D. A functional assay for centromere-associated sister chromatid cohesion. Science 285, 254-257 (1999).
94. Losada, A. & Hirano, T. Biology in pictures: new light on sticky sisters. Curr. Biol. 10, 615 (2000).
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).
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).
97. Pasierbek, P. et al. A Caenorhabditis elegans cohesion protein with functions in meiotic chromosome pairing and disfunction. Genes Dev. 15, 1349-1360 (2001).
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).
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).
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).
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).
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).
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).
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).
105. Swedlow, J. R. & Hirano, T. The making of the mitotic chromosome: modern insights into classical questions. Mol. Cell 11, 557-569 (2003).
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).
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).
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).
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).