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* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)
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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)1508-1519.e18
Number of pages31
Issue number6
Early online date10 May 2018
Publication statusPublished - 31 May 2018

Bibliographical note

We are grateful to Katsuhiko Shirahige, Julian Blow, Tatsuro Takahashi, and
Rob Klose for supplying antibodies and to Byung-Gil Lee and Jan Lo¨ we for
sharing plasmids and protocols. We thank all members of the Nasmyth group
for valuable discussions and technical assistance, in particular Jean Metson
and Antonio Valde´ s Gutie´rrez. This work was funded by the Wellcome Trust
(107935/Z/15/Z to K.A.N.), European Research Council (294401 to K.A.N.),
Cancer Research UK (C573/A 12386 to K.A.N.), and Medical Research Council
(MR/L018047/1 to K.A.N.). V.C. is funded by the Associazione Italiana per la
Ricerca sul Cancro (AIRC) IG 17087, the ERC (614541), the Giovanni Armenise-Harvard foundation award, and Epigen Progetto Bandiera 4.7


  • loop extrusion
  • sister chromatid cohesion
  • condensin
  • SMC
  • chromosome condensation


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