Structural Studies Reveal the Functional Modularity of the Scc2-Scc4 Cohesin Loader
The remarkable accuracy of eukaryotic cell division is partly maintained by the cohesin complex acting as a molecular glue to prevent premature sister chromatid separation. The loading of cohesin onto chromosomes is catalyzed by the Scc2-Scc4 loader complex. Here, we report the crystal structure of...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-08-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715007093 |
| _version_ | 1819264289257553920 |
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| author | William C.H. Chao Yasuto Murayama Sofía Muñoz Alessandro Costa Frank Uhlmann Martin R. Singleton |
| author_facet | William C.H. Chao Yasuto Murayama Sofía Muñoz Alessandro Costa Frank Uhlmann Martin R. Singleton |
| author_sort | William C.H. Chao |
| collection | DOAJ |
| description | The remarkable accuracy of eukaryotic cell division is partly maintained by the cohesin complex acting as a molecular glue to prevent premature sister chromatid separation. The loading of cohesin onto chromosomes is catalyzed by the Scc2-Scc4 loader complex. Here, we report the crystal structure of Scc4 bound to the N terminus of Scc2 and show that Scc4 is a tetratricopeptide repeat (TPR) superhelix. The Scc2 N terminus adopts an extended conformation and is entrapped by the core of the Scc4 superhelix. Electron microscopy (EM) analysis reveals that the Scc2-Scc4 loader complex comprises three domains: a head, body, and hook. Deletion studies unambiguously assign the Scc2N-Scc4 as the globular head domain, whereas in vitro cohesin loading assays show that the central body and the hook domains are sufficient to catalyze cohesin loading onto circular DNA, but not chromatinized DNA in vivo, suggesting a possible role for Scc4 as a chromatin adaptor. |
| first_indexed | 2024-12-23T20:27:07Z |
| format | Article |
| id | doaj.art-1a897e8fe0834d34996d0e051f02d7ee |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-23T20:27:07Z |
| publishDate | 2015-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-1a897e8fe0834d34996d0e051f02d7ee2022-12-21T17:32:20ZengElsevierCell Reports2211-12472015-08-0112571972510.1016/j.celrep.2015.06.071Structural Studies Reveal the Functional Modularity of the Scc2-Scc4 Cohesin LoaderWilliam C.H. Chao0Yasuto Murayama1Sofía Muñoz2Alessandro Costa3Frank Uhlmann4Martin R. Singleton5Lincoln’s Inn Fields Laboratory, The Francis Crick Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UKLincoln’s Inn Fields Laboratory, The Francis Crick Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UKLincoln’s Inn Fields Laboratory, The Francis Crick Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UKClare Hall Laboratory, The Francis Crick Institute, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, UKLincoln’s Inn Fields Laboratory, The Francis Crick Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UKLincoln’s Inn Fields Laboratory, The Francis Crick Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UKThe remarkable accuracy of eukaryotic cell division is partly maintained by the cohesin complex acting as a molecular glue to prevent premature sister chromatid separation. The loading of cohesin onto chromosomes is catalyzed by the Scc2-Scc4 loader complex. Here, we report the crystal structure of Scc4 bound to the N terminus of Scc2 and show that Scc4 is a tetratricopeptide repeat (TPR) superhelix. The Scc2 N terminus adopts an extended conformation and is entrapped by the core of the Scc4 superhelix. Electron microscopy (EM) analysis reveals that the Scc2-Scc4 loader complex comprises three domains: a head, body, and hook. Deletion studies unambiguously assign the Scc2N-Scc4 as the globular head domain, whereas in vitro cohesin loading assays show that the central body and the hook domains are sufficient to catalyze cohesin loading onto circular DNA, but not chromatinized DNA in vivo, suggesting a possible role for Scc4 as a chromatin adaptor.http://www.sciencedirect.com/science/article/pii/S2211124715007093 |
| spellingShingle | William C.H. Chao Yasuto Murayama Sofía Muñoz Alessandro Costa Frank Uhlmann Martin R. Singleton Structural Studies Reveal the Functional Modularity of the Scc2-Scc4 Cohesin Loader Cell Reports |
| title | Structural Studies Reveal the Functional Modularity of the Scc2-Scc4 Cohesin Loader |
| title_full | Structural Studies Reveal the Functional Modularity of the Scc2-Scc4 Cohesin Loader |
| title_fullStr | Structural Studies Reveal the Functional Modularity of the Scc2-Scc4 Cohesin Loader |
| title_full_unstemmed | Structural Studies Reveal the Functional Modularity of the Scc2-Scc4 Cohesin Loader |
| title_short | Structural Studies Reveal the Functional Modularity of the Scc2-Scc4 Cohesin Loader |
| title_sort | structural studies reveal the functional modularity of the scc2 scc4 cohesin loader |
| url | http://www.sciencedirect.com/science/article/pii/S2211124715007093 |
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