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Nat Struct Mol Biol. 2014 Oct;21(10):864-70. doi: 10.1038/nsmb.2880. Epub 2014 Aug 31.

Structure of cohesin subcomplex pinpoints direct shugoshin-Wapl antagonism in centromeric cohesion.

Author information

1
1] Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. [2] [3].
2
1] Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. [2].
3
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
4
1] Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. [2] Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
5
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Abstract

Orderly termination of sister-chromatid cohesion during mitosis is critical for accurate chromosome segregation. During prophase, mitotic kinases phosphorylate cohesin and its protector sororin, triggering Wapl-dependent cohesin release from chromosome arms. The shugoshin (Sgo1)-PP2A complex protects centromeric cohesin until its cleavage by separase at anaphase onset. Here, we report the crystal structure of a human cohesin subcomplex comprising SA2 and Scc1. Multiple HEAT repeats of SA2 form a dragon-shaped structure. Scc1 makes extensive contacts with SA2, with one binding hotspot. Sgo1 and Wapl compete for binding to a conserved site on SA2-Scc1. At this site, mutations of SA2 residues that disrupt Wapl binding bypass the Sgo1 requirement in cohesion protection. Thus, in addition to recruiting PP2A to dephosphorylate cohesin and sororin, Sgo1 physically shields cohesin from Wapl. This unexpected, direct antagonism between Sgo1 and Wapl augments centromeric cohesion protection.

PMID:
25173175
PMCID:
PMC4190070
DOI:
10.1038/nsmb.2880
[Indexed for MEDLINE]
Free PMC Article
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