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Both interaction surfaces within cohesin's hinge domain are essential for its stable chromosomal association

Both interaction surfaces within cohesin's hinge domain are essential for its stable chromosomal association
Both interaction surfaces within cohesin's hinge domain are essential for its stable chromosomal association
Background
The cohesin complex that mediates sister chromatid cohesion contains three core subunits: Smc1, Smc3, and Scc1. Heterotypic interactions between Smc1 and Smc3 dimerization domains create stable V-shaped Smc1/Smc3 heterodimers with a hinge at the center and nucleotide-binding domains (NBDs) at the ends of each arm. Interconnection of each NBD through their association with the N- and C-terminal domains of Scc1 creates a tripartite ring, within which sister DNAs are thought to be entrapped (the ring model). Crystal structures show that the Smc1/Smc3 hinge has a toroidal shape, with independent “north” and “south” interaction surfaces on an axis of pseudosymmetry. The ring model predicts that sister chromatid cohesion would be lost by transient hinge opening.

Results
We find that mutations within either interface weaken heterodimerization of isolated half hinges in vitro but do not greatly compromise formation of cohesin rings in vivo. They do, however, reduce the residence time of cohesin on chromosomes and cause lethal defects in sister chromatid cohesion. This demonstrates that mere formation of rings is insufficient for cohesin function. Stable cohesion requires cohesin rings that cannot easily open.

Conclusions
Either the north or south hinge interaction surface is sufficient for the assembly of V-shaped Smc1/Smc3 heterodimers in vivo. Any tendency of Smc proteins with weakened hinges to dissociate will be suppressed by interconnection of their NBDs by Scc1. We suggest that transient hinge dissociation caused by the mutations described here is incompatible with stable sister chromatid cohesion because it permits chromatin fibers to escape from cohesin rings.

Highlights
Unstable Smc1/3 hinge dimerization reduces the residence time of cohesin on chromatin

DNA
0960-9822
279-289
Mishra, Ajay
d7ab328b-f7b9-4985-8be7-24f90228bba9
Hu, Bin
7648bcc3-417f-4784-b141-26f96b174998
Kurze, Alexander
370c85c2-6174-401e-94d4-1accea932701
Beckouët, Frédéric
eb0a3083-2ac7-456d-88c6-36b5d4908f58
Farcas, Ana-Maria
b88b360a-ea17-4ab2-88d5-4ee92c890fce
Dixon, Sarah E
25e82398-5590-4f16-aa74-4ab72770047a
Katou, Yuki
1716a81b-b2b6-4606-be18-2054362bfea3
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
Shirahige, Katsuhiko
82f2ad12-bc87-4239-b0ae-bf2e4c8f4480
Nasmyth, Kim
c6f3acaf-79ff-4d0d-be29-42d41e842ded
Mishra, Ajay
d7ab328b-f7b9-4985-8be7-24f90228bba9
Hu, Bin
7648bcc3-417f-4784-b141-26f96b174998
Kurze, Alexander
370c85c2-6174-401e-94d4-1accea932701
Beckouët, Frédéric
eb0a3083-2ac7-456d-88c6-36b5d4908f58
Farcas, Ana-Maria
b88b360a-ea17-4ab2-88d5-4ee92c890fce
Dixon, Sarah E
25e82398-5590-4f16-aa74-4ab72770047a
Katou, Yuki
1716a81b-b2b6-4606-be18-2054362bfea3
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
Shirahige, Katsuhiko
82f2ad12-bc87-4239-b0ae-bf2e4c8f4480
Nasmyth, Kim
c6f3acaf-79ff-4d0d-be29-42d41e842ded

Mishra, Ajay, Hu, Bin, Kurze, Alexander, Beckouët, Frédéric, Farcas, Ana-Maria, Dixon, Sarah E, Katou, Yuki, Khalid, Syma, Shirahige, Katsuhiko and Nasmyth, Kim (2010) Both interaction surfaces within cohesin's hinge domain are essential for its stable chromosomal association. Current Biology, 20 (4), 279-289. (doi:10.1016/j.cub.2009.12.059).

Record type: Article

Abstract

Background
The cohesin complex that mediates sister chromatid cohesion contains three core subunits: Smc1, Smc3, and Scc1. Heterotypic interactions between Smc1 and Smc3 dimerization domains create stable V-shaped Smc1/Smc3 heterodimers with a hinge at the center and nucleotide-binding domains (NBDs) at the ends of each arm. Interconnection of each NBD through their association with the N- and C-terminal domains of Scc1 creates a tripartite ring, within which sister DNAs are thought to be entrapped (the ring model). Crystal structures show that the Smc1/Smc3 hinge has a toroidal shape, with independent “north” and “south” interaction surfaces on an axis of pseudosymmetry. The ring model predicts that sister chromatid cohesion would be lost by transient hinge opening.

Results
We find that mutations within either interface weaken heterodimerization of isolated half hinges in vitro but do not greatly compromise formation of cohesin rings in vivo. They do, however, reduce the residence time of cohesin on chromosomes and cause lethal defects in sister chromatid cohesion. This demonstrates that mere formation of rings is insufficient for cohesin function. Stable cohesion requires cohesin rings that cannot easily open.

Conclusions
Either the north or south hinge interaction surface is sufficient for the assembly of V-shaped Smc1/Smc3 heterodimers in vivo. Any tendency of Smc proteins with weakened hinges to dissociate will be suppressed by interconnection of their NBDs by Scc1. We suggest that transient hinge dissociation caused by the mutations described here is incompatible with stable sister chromatid cohesion because it permits chromatin fibers to escape from cohesin rings.

Highlights
Unstable Smc1/3 hinge dimerization reduces the residence time of cohesin on chromatin

Full text not available from this repository.

More information

Published date: 23 February 2010
Keywords: DNA

Identifiers

Local EPrints ID: 149537
URI: http://eprints.soton.ac.uk/id/eprint/149537
ISSN: 0960-9822
PURE UUID: 233d4ef8-65b5-4d57-943e-fa7050283bad
ORCID for Syma Khalid: ORCID iD orcid.org/0000-0002-3694-5044

Catalogue record

Date deposited: 30 Apr 2010 13:09
Last modified: 10 Dec 2019 01:42

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Contributors

Author: Ajay Mishra
Author: Bin Hu
Author: Alexander Kurze
Author: Frédéric Beckouët
Author: Ana-Maria Farcas
Author: Sarah E Dixon
Author: Yuki Katou
Author: Syma Khalid ORCID iD
Author: Katsuhiko Shirahige
Author: Kim Nasmyth

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