The cohesin ring uses its hinge to organize DNA using non-topological as well as topological mechanisms

Srinivasan, Madhusudhan, Scheinost, Johanna C, Petela, Naomi J, Gligoris, Thomas G, Wissler, Maria, Ogushi, Sugako, Collier, James E, Voulgaris, Menelaos, Kurze, Alexander, Chan, Kok-Lung, Hu, Bin, Constanzo, Vincenzo and Nasmyth, Kim A (2018) The cohesin ring uses its hinge to organize DNA using non-topological as well as topological mechanisms. Cell. ISSN 1097-4172

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Abstract

As predicted by the notion that sister chromatid cohesion is mediated by entrapment of sister DNAs inside cohesin rings, there is perfect correlation between co-entrapment of circular minichromosomes and sister chromatid cohesion. In most cells where cohesin loads without conferring cohesion, it does so by entrapment of individual DNAs. However, cohesin with a hinge domain whose positively charged lumen is neutralized loads and moves along chromatin despite failing to entrap DNAs. Thus, cohesin engages chromatin in non-topological, as well as topological, manners. Since hinge mutations, but not Smc-kleisin fusions, abolish entrapment, DNAs may enter cohesin rings through hinge opening. Mutation of three highly conserved lysine residues inside the Smc1 moiety of Smc1/3 hinges abolishes all loading without affecting cohesin’s recruitment to CEN loading sites or its ability to hydrolyze ATP. We suggest that loading and translocation are mediated by conformational changes in cohesin’s hinge driven by cycles of ATP hydrolysis.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Research Centres and Groups: Genome Damage and Stability Centre
Depositing User: Paula Amiet-West
Date Deposited: 23 May 2018 09:17
Last Modified: 23 May 2018 09:22
URI: http://srodev.sussex.ac.uk/id/eprint/75953

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