Both interaction surfaces within cohesin's hinge domain are essential for its stable chromosomal association
| Autor: | Syma Khalid, Katsuhiko Shirahige, Alexander Kurze, Bin Hu, Ana-Maria Farcas, Yuki Katou, Kim Nasmyth, Sarah E. Dixon, Ajay Kumar Mishra, Frédéric Beckouët |
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| Přispěvatelé: | Laboratoire de biologie moléculaire eucaryote (LBME), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Models
Molecular Cohesin complex Chromosomal Proteins Non-Histone [SDV]Life Sciences [q-bio] Molecular Sequence Data Hinge Cell Cycle Proteins Biology Chromatids General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine Species Specificity Yeasts Amino Acid Sequence ComputingMilieux_MISCELLANEOUS 030304 developmental biology Genetics 0303 health sciences Agricultural and Biological Sciences(all) Cohesin Biochemistry Genetics and Molecular Biology(all) SMC protein DNA 3. Good health Chromatin Protein Structure Tertiary Establishment of sister chromatid cohesion Schizosaccharomyces pombe Proteins Mutation Biophysics Chromatography Gel Chromatid biological phenomena cell phenomena and immunity General Agricultural and Biological Sciences Crystallization Dimerization 030217 neurology & neurosurgery |
| Zdroj: | Current Biology-CB Current Biology-CB, Elsevier, 2010, 20 (4), pp.279-289. ⟨10.1016/j.cub.2009.12.059⟩ Current Biology |
| ISSN: | 1879-0445 0960-9822 |
| DOI: | 10.1016/j.cub.2009.12.059⟩ |
| Popis: | Summary Background The cohesin complex that mediates sister chromatid cohesion contains three core subunits: Smc1, Smc3, and Scc1. Heterotypic interactions between Smc1 and Smc3 dimerization domains create stable V-shaped Smc1/Smc3 heterodimers with a hinge at the center and nucleotide-binding domains (NBDs) at the ends of each arm. Interconnection of each NBD through their association with the N- and C-terminal domains of Scc1 creates a tripartite ring, within which sister DNAs are thought to be entrapped (the ring model). Crystal structures show that the Smc1/Smc3 hinge has a toroidal shape, with independent “north” and “south” interaction surfaces on an axis of pseudosymmetry. The ring model predicts that sister chromatid cohesion would be lost by transient hinge opening. Results We find that mutations within either interface weaken heterodimerization of isolated half hinges in vitro but do not greatly compromise formation of cohesin rings in vivo. They do, however, reduce the residence time of cohesin on chromosomes and cause lethal defects in sister chromatid cohesion. This demonstrates that mere formation of rings is insufficient for cohesin function. Stable cohesion requires cohesin rings that cannot easily open. Conclusions Either the north or south hinge interaction surface is sufficient for the assembly of V-shaped Smc1/Smc3 heterodimers in vivo. Any tendency of Smc proteins with weakened hinges to dissociate will be suppressed by interconnection of their NBDs by Scc1. We suggest that transient hinge dissociation caused by the mutations described here is incompatible with stable sister chromatid cohesion because it permits chromatin fibers to escape from cohesin rings. Highlights ► Unstable Smc1/3 hinge dimerization reduces the residence time of cohesin on chromatin |
| Databáze: | OpenAIRE |
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