Journal
EMBO REPORTS
Volume 22, Issue 7, Pages -Publisher
WILEY
DOI: 10.15252/embr.202052295
Keywords
cohesin; mitosis; phosphatase; PP2A‐ B56; shugoshin
Categories
Funding
- Danish Cancer Society [R167- A10951-17-S2]
- Independent Research Fund Denmark [8021-00101B]
- Novo Nordisk Foundation [NNF18OC0053124]
- Swiss National Fund [P2EZP3_178624]
- Danish Lundbeckfonden [2017-3212]
- NIH/NIGMS [R35GM119455]
- NIH [S10-OD016212]
- Dutch Cancer Society
- Dutch Cancer Society [10366]
- Wellcome Trust [095822, 202811]
- Darwin Trust of Edinburgh
- cryo-EM grant [NNF0024386]
- cryoNET grant [NNF17SA0030214]
- [NNF14CC0001]
- Swiss National Science Foundation (SNF) [P2EZP3_178624] Funding Source: Swiss National Science Foundation (SNF)
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The study reveals the structure and function of the PP2A-B56-hSgo1 complex during mitosis, highlighting the essential role of a conserved pocket on the B56 regulatory subunit for hSgo1 binding and cohesion protection. Additionally, it shows that hSgo1 inhibits the binding of PP2A-B56 substrates and that PP2A-B56 dephosphorylates Cdk1 sites on hSgo1 to regulate cohesin interactions. Overall, the research provides important insights into cohesion protection during mitosis.
The shugoshin proteins are universal protectors of centromeric cohesin during mitosis and meiosis. The binding of human hSgo1 to the PP2A-B56 phosphatase through a coiled-coil (CC) region mediates cohesion protection during mitosis. Here we undertook a structure function analysis of the PP2A-B56-hSgo1 complex, revealing unanticipated aspects of complex formation and function. We establish that a highly conserved pocket on the B56 regulatory subunit is required for hSgo1 binding and cohesion protection during mitosis in human somatic cells. Consistent with this, we show that hSgo1 blocks the binding of PP2A-B56 substrates containing a canonical B56 binding motif. We find that PP2A-B56 bound to hSgo1 dephosphorylates Cdk1 sites on hSgo1 itself to modulate cohesin interactions. Collectively our work provides important insight into cohesion protection during mitosis.
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