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

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 journal › Article › peer-review

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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 language	English
Pages (from-to)	1508-1519.e18
Number of pages	31
Journal	Cell
Volume	173
Issue number	6
Early online date	10 May 2018
DOIs	https://doi.org/10.1016/j.cell.2018.04.015
Publication status	Published - 31 May 2018

Bibliographical note

ACKNOWLEDGMENTS
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

Keywords

loop extrusion
sister chromatid cohesion
condensin
SMC
chromosome condensation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Srinivasan-et-al-cohesin-ring-cell-vor
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Final published version, 4.75 MBLicence: CC BY

Cite this

@article{277ab3830a8f48c1b3e5f8ed8a671aed,

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

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 doesso 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 notSmc-kleisin fusions, abolish entrapment, DNAs may enter cohesin rings through hinge opening. Mutation of three highly conserved lysine residues inside theSmc1 moiety of Smc1/3 hinges abolishes all loading without affecting cohesin{\textquoteright}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{\textquoteright}s hinge driven by cycles of ATP hydrolysis.",

keywords = "loop extrusion, sister chromatid cohesion, condensin, SMC, chromosome condensation",

author = "Madhusudhan Srinivasan and Scheinost, {Johanna C.} and Petela, {Naomi J.} and Gligoris, {Thomas G.} and Maria Wissler and Sugako Ogushi and Collier, {James E.} and Menelaos Voulgaris and Alexander Kurze and Kok-Lung Chan and Bin Hu and Vincenzo Costanzo and Nasmyth, {Kim A.}",

note = "ACKNOWLEDGMENTS 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",

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doi = "10.1016/j.cell.2018.04.015",

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T1 - The Cohesin Ring Uses Its Hinge to Organize DNA Using Non-topological as well as Topological Mechanisms

AU - Srinivasan, Madhusudhan

AU - Scheinost, Johanna C.

AU - Petela, Naomi J.

AU - Gligoris, Thomas G.

AU - Wissler, Maria

AU - Ogushi, Sugako

AU - Collier, James E.

AU - Voulgaris, Menelaos

AU - Kurze, Alexander

AU - Chan, Kok-Lung

AU - Hu, Bin

AU - Costanzo, Vincenzo

AU - Nasmyth, Kim A.

N1 - ACKNOWLEDGMENTS 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

PY - 2018/5/31

Y1 - 2018/5/31

N2 - 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 doesso 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 notSmc-kleisin fusions, abolish entrapment, DNAs may enter cohesin rings through hinge opening. Mutation of three highly conserved lysine residues inside theSmc1 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.

AB - 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 doesso 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 notSmc-kleisin fusions, abolish entrapment, DNAs may enter cohesin rings through hinge opening. Mutation of three highly conserved lysine residues inside theSmc1 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.

KW - loop extrusion

KW - sister chromatid cohesion

KW - condensin

KW - SMC

KW - chromosome condensation

UR - http://europepmc.org/abstract/med/29754816

U2 - 10.1016/j.cell.2018.04.015

DO - 10.1016/j.cell.2018.04.015

M3 - Article

C2 - 29754816

SN - 0092-8674

VL - 173

SP - 1508-1519.e18

JO - Cell

JF - Cell

IS - 6

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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Bin Hu

Cite this

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Profiles

Bin Hu

Cite this