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The Cohesin Ring Uses Its Hinge to Organize DNA Using Non-topological as well as Topological Mechanisms

2018; Cell Press; Volume: 173; Issue: 6 Linguagem: Inglês

10.1016/j.cell.2018.04.015

1097-4172

Madhusudhan Srinivasan, Johanna C. Scheinost, Naomi J Petela, Thomas G. Gligoris, Maria Wissler, Sugako Ogushi, James E. Collier, Menelaos Voulgaris, Alexander Kurze, Kok‐Lung Chan, Bin Hu, Vincenzo Costanzo, Kim Nasmyth,

RNA and protein synthesis mechanisms

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.