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A highly conserved pocket on PP2A‐B56 is required for hSgo1 binding and cohesion protection during mitosis
Author(s) -
Ueki Yumi,
Hadders Michael A,
Weisser Melanie B,
Nasa Isha,
SoteloParrilla Paula,
Cressey Lauren E,
Gupta Tanmay,
Hertz Emil P T,
Kruse Thomas,
Montoya Guillermo,
Jeyaprakash A Arockia,
Kettenbach Arminja,
Lens Susanne M A,
Nilsson Jakob
Publication year - 2021
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202052295
Subject(s) - cohesin , protein phosphatase 2 , mitosis , microbiology and biotechnology , biology , coiled coil , chromosome segregation , protein subunit , genetics , meiosis , phosphatase , phosphorylation , chromosome , gene
Abstract 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.