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

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 A Nasmyth

doi:10.1016/j.cell.2018.04.015

Madhusudhan Srinivasan, Johanna C Scheinost + Show 11 more

Open Access

https://doi.org/10.1016/j.cell.2018.04.015

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Abstract

SummaryAs 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.

Highlights

Smc/kleisin complexes facilitate chromosome segregation in bacteria as well as eukaryotes (Schleiffer et al, 2003)
We found that co-entrapment of sister DNAs within cohesin rings invariably accompanies sister chromatid cohesion
Organization of DNA into Chromatid-like Threads Does Not Require Entrapment of DNA by Cohesin Rings We addressed whether smc1DDsmc3AAA cohesin is still active in organizing chromosome topology

Summary

Introduction

Smc/kleisin complexes facilitate chromosome segregation in bacteria as well as eukaryotes (Schleiffer et al, 2003) The latter have three types: condensin, cohesin, and the Smc5/6 complex (Haering and Gruber, 2016). Smc and Smc are rod-shaped proteins containing 50-nmlong intra-molecular anti-parallel coiled coils with a hinge/dimerization domain at one end and an ABC-like ATPase head domain composed of the protein’s N- and C-terminal sequences at the other. They bind each other via their hinges to form V-shaped heterodimers whose apical ATPases are interconnected by a single Scc polypeptide (Gruber et al, 2003). Bacterial Smc/kleisin complexes form similar structures, suggesting that asymmetric ring formation is a universal feature (Burmann et al, 2013)

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