Haering, Christian H. , Farcas, Ana-Maria , Arumugam, Prakash , Metson, Jean and Nasmyth, Kim . (2008) The cohesin ring concatenates sister DNA molecules. Nature, Vol.454 . pp. 297-301. ISSN 0028-0836

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Abstract

Sister chromatid cohesion, which is essential for mitosis, is mediated by a multi-subunit protein complex called cohesin whose Scc1, Smc1, and Smc3 subunits form a tripartite ring structure. It has been proposed that cohesin holds sister DNAs together by trapping them inside its ring. To test this, we used site-specific cross-linking to create chemical connections at the three interfaces between the ring’s three constituent polypeptides, thereby creating covalently closed cohesin rings. As predicted by the ring entrapment model, this procedure produces dimeric DNA/cohesin structures that are resistant to protein denaturation. We conclude that cohesin rings concatenate individual sister minichromosome DNAs.

Item Type:	Journal Article
Subjects:	Q Science > QR Microbiology
Divisions:	Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH):	DNA
Journal or Publication Title:	Nature
Publisher:	Nature Publishing
ISSN:	0028-0836
Date:	2 July 2008
Volume:	Vol.454
Page Range:	pp. 297-301
Identification Number:	10.1038/nature07098
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Description:	Version accepted by publisher (post-print, after peer review, before copy-editing).
Funder:	Medical Research Council (Great Britain) (MRC), Wellcome Trust (London, England), Cancer Research UK (CRUK)
References:	1 Nasmyth, K. & Haering, C. H. The structure and function of SMC and kleisin complexes. Annu Rev Biochem 74, 595-648 (2005). 2 Hirano, T. SMC proteins and chromosome mechanics: from bacteria to humans. Philosophical transactions of the Royal Society of London 360 (1455), 507-514 (2005). 3 Uhlmann, F. et al. Cleavage of cohesin by the CD clan protease separin triggers anaphase in yeast. Cell 103, 375-386 (2000). 4 Haering, C. H., Lowe, J., Hochwagen, A., & Nasmyth, K. Molecular Architecture of SMC Proteins and the Yeast Cohesin Complex. Mol Cell 9 (4), 773-788. (2002). 5 Hirano, M. & Hirano, T. Hinge-mediated dimerization of SMC protein is essential for its dynamic interaction with DNA. EMBO J 21, 5733-5744 (2002). 6 Gruber, S., Haering, C. H., & Nasmyth, K. Chromosomal cohesin forms a ring. Cell 112 (6), 765-777 (2003). 7 Ivanov, D. & Nasmyth, K. A physical assay for sister chromatid cohesion in vitro. Mol Cell 27 (2), 300-310 (2007). 8 Milutinovich, M. & Koshland, D. E. Molecular biology. SMC complexes--wrapped up in controversy. Science 300 (5622), 1101-1102 (2003). 9 Kim, J. S. & Raines, R. T. Dibromobimane as a fluorescent crosslinking reagent. Analytical biochemistry 225 (1), 174-176 (1995). 10 Dhar, G., Sanders, E. R., & Johnson, R. C. Architecture of the hin synaptic complex during recombination: the recombinase subunits translocate with the DNA strands. Cell 119 (1), 33-45 (2004). 11 Eswar, N. et al. in Current Protocols in Bioinformatics (John Wiley & Sons, Inc., 2006), Vol. Supplement 15, 5.6.1-5.6.30, 200. 12 Haering, C. H. et al. Structure and stability of cohesin's Smc1-kleisin interaction. Mol Cell 15 (6), 951-964 (2004). 13 Gruber, S. et al. Evidence that loading of cohesin onto chromosomes involves opening of its SMC hinge. Cell 127 (3), 523-537 (2006). 14 Bausch, C. et al. Transcription alters chromosomal locations of cohesin in Saccharomyces cerevisiae. Molecular and cellular biology 27 (24), 8522-8532 (2007). 15 Schuldiner, O. et al. piggyBac-Based Mosaic Screen Identifies a Postmitotic Function for Cohesin in Regulating Developmental Axon Pruning. Developmental cell 14 (2), 227-238 (2008). 16 Pauli, A. et al. Cell-Type-Specific TEV Protease Cleavage Reveals Cohesin Functions in Drosophila Neurons. Developmental cell 14 (2), 239-251 (2008). 17 Megee, P. C. & Koshland, D. A functional assay for centromere-associated sister chromatid cohesion. Science 285 (5425), 254-257 (1999). 18 Hwang, D. C. et al. Characterization of active-site residues of the NIa protease from tobacco vein mottling virus. Molecules and cells 10 (5), 505-511 (2000).
URI:	http://wrap.warwick.ac.uk/id/eprint/207

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