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

M Srinivasan, JC Scheinost, NJ Petela, TG Gligoris, M Wissler, S Ogushi, JE Collier, M Voulgaris, A Kurze, KL Chan, B Hu, V Costanzo, KA Nasmyth

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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.
Original languageEnglish
Pages (from-to)105-119, e1-e9
Number of pages30
JournalCell
Volume173
Early online date10 May 2018
DOIs
Publication statusPublished - 31 May 2018

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    Srinivasan, M., Scheinost, JC., Petela, NJ., Gligoris, TG., Wissler, M., Ogushi, S., Collier, JE., Voulgaris, M., Kurze, A., Chan, KL., Hu, B., Costanzo, V., & Nasmyth, KA. (2018). The Cohesin Ring Uses Its Hinge to Organize DNA Using Non-topological as well as Topological Mechanisms. Cell, 173, 105-119, e1-e9. https://doi.org/10.1016/j.cell.2018.04.015