A highly conserved pocket on PP2A-B56 is required for hSgo1 binding and cohesion protection during mitosis

Yumi Ueki; Michael A. Hadders; Melanie B. Weisser; Isha Nasa; Paula Sotelo-Parrilla; Lauren E. Cressey; Tanmay Gupta; Emil P.T. Hertz; Thomas Kruse; Guillermo Montoya; A. Arockia Jeyaprakash; Arminja Kettenbach; Susanne M.A. Lens; Jakob Nilsson

doi:10.15252/embr.202052295

A highly conserved pocket on PP2A-B56 is required for hSgo1 binding and cohesion protection during mitosis

Yumi Ueki, Michael A. Hadders, Melanie B. Weisser, Isha Nasa, Paula Sotelo-Parrilla, Lauren E. Cressey, Tanmay Gupta, Emil P.T. Hertz, Thomas Kruse, Guillermo Montoya, A. Arockia Jeyaprakash, Arminja Kettenbach, Susanne M.A. Lens, Jakob Nilsson^*

^*Corresponding author for this work

School of Biological Sciences

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Article number	e52295
Number of pages	13
Journal	EMBO Reports
Volume	22
Issue number	7
Early online date	11 May 2021
DOIs	https://doi.org/10.15252/embr.202052295
Publication status	Published - 5 Jul 2021

Keywords / Materials (for Non-textual outputs)

cohesin
mitosis
phosphatase
PP2A-B56
shugoshin

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10.15252/embr.202052295Licence: Creative Commons: Attribution (CC-BY)

NilssonEtalEMBO2021AHighlyConservedPocketOnPP2A-B56Final published version, 4.03 MBLicence: Creative Commons: Attribution (CC-BY)

Molecular Mechanisms of Centromere Inheritance and Kinetochore Function
Arulanandam, J.
UK-based charities
4/01/17 → 4/10/22
Project: Research
Molecular and Structural Basis for the Centromeric Localisation and Function of the CPC in Achieving Faithful Chromosome Segregation
Arulanandam, J.
UK-based charities
21/01/15 → 20/01/17
Project: Research
Structural basis for stable kinetochore-microtubule attachments and timely onset of anaphase by the Ska complex
Arulanandam, J.
UK-based charities
4/01/12 → 3/01/17
Project: Research

Cite this

Ueki, Y., Hadders, M. A., Weisser, M. B., Nasa, I., Sotelo-Parrilla, P., Cressey, L. E., Gupta, T., Hertz, E. P. T., Kruse, T., Montoya, G., Jeyaprakash, A. A., Kettenbach, A., Lens, S. M. A., & Nilsson, J. (2021). A highly conserved pocket on PP2A-B56 is required for hSgo1 binding and cohesion protection during mitosis. EMBO Reports, 22(7), Article e52295. https://doi.org/10.15252/embr.202052295

@article{775e7aaf040742fdacaf3b88f4cf2248,

title = "A highly conserved pocket on PP2A-B56 is required for hSgo1 binding and cohesion protection during mitosis",

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.",

keywords = "cohesin, mitosis, phosphatase, PP2A-B56, shugoshin",

author = "Yumi Ueki and Hadders, {Michael A.} and Weisser, {Melanie B.} and Isha Nasa and Paula Sotelo-Parrilla and Cressey, {Lauren E.} and Tanmay Gupta and Hertz, {Emil P.T.} and Thomas Kruse and Guillermo Montoya and Jeyaprakash, {A. Arockia} and Arminja Kettenbach and Lens, {Susanne M.A.} and Jakob Nilsson",

year = "2021",

month = jul,

day = "5",

doi = "10.15252/embr.202052295",

language = "English",

volume = "22",

journal = "EMBO Reports",

issn = "1469-221X",

publisher = "Wiley",

number = "7",

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TY - JOUR

T1 - A highly conserved pocket on PP2A-B56 is required for hSgo1 binding and cohesion protection during mitosis

AU - Ueki, Yumi

AU - Hadders, Michael A.

AU - Weisser, Melanie B.

AU - Nasa, Isha

AU - Sotelo-Parrilla, Paula

AU - Cressey, Lauren E.

AU - Gupta, Tanmay

AU - Hertz, Emil P.T.

AU - Kruse, Thomas

AU - Montoya, Guillermo

AU - Jeyaprakash, A. Arockia

AU - Kettenbach, Arminja

AU - Lens, Susanne M.A.

AU - Nilsson, Jakob

PY - 2021/7/5

Y1 - 2021/7/5

N2 - 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.

AB - 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.

KW - cohesin

KW - mitosis

KW - phosphatase

KW - PP2A-B56

KW - shugoshin

U2 - 10.15252/embr.202052295

DO - 10.15252/embr.202052295

M3 - Article

AN - SCOPUS:85105652503

SN - 1469-221X

VL - 22

JO - EMBO Reports

JF - EMBO Reports

IS - 7

M1 - e52295

ER -

A highly conserved pocket on PP2A-B56 is required for hSgo1 binding and cohesion protection during mitosis

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Keywords / Materials (for Non-textual outputs)

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Projects

Molecular Mechanisms of Centromere Inheritance and Kinetochore Function

Molecular and Structural Basis for the Centromeric Localisation and Function of the CPC in Achieving Faithful Chromosome Segregation

Structural basis for stable kinetochore-microtubule attachments and timely onset of anaphase by the Ska complex

Cite this