Scc2 Is a Potent Activator of Cohesin’s ATPase that Promotes Loading by Binding Scc1 without Pds5

Naomi J. Petela; Thomas G. Gligoris; Jean Metson; Byung-Gil Lee; Menelaos Voulgaris; Bin Hu; Sotaro Kikuchi; Christophe Chapard; Wentao Chen; Eeson Rajendra; Madhusudhan Srinivisan; Hongtao Yu; Jan Löwe; Kim A. Nasmyth

doi:10.1016/j.molcel.2018.05.022

Scc2 Is a Potent Activator of Cohesin’s ATPase that Promotes Loading by Binding Scc1 without Pds5

Naomi J. Petela, Thomas G. Gligoris, Jean Metson, Byung-Gil Lee, Menelaos Voulgaris, Bin Hu, Sotaro Kikuchi, Christophe Chapard, Wentao Chen, Eeson Rajendra, Madhusudhan Srinivisan, Hongtao Yu, Jan Löwe, Kim A. Nasmyth^* (Corresponding Author)

^*Corresponding author for this work

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

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Abstract

Cohesin organizes DNA into chromatids, regulates enhancer-promoter interactions, and confers sister chromatid cohesion. Its association with chromosomes is regulated by hook-shaped HEAT repeat proteins that bind Scc1, namely Scc3, Pds5, and Scc2. Unlike Pds5, Scc2 is not a stable cohesin constituent but, as shown here, transiently replaces Pds5. Scc1 mutations that compromise its interaction with Scc2 adversely affect cohesin’s ATPase activity and loading. Moreover, Scc2 mutations that alter how the ATPase responds to DNA abolish loading despite cohesin’s initial association with loading sites. Lastly, Scc2 mutations that permit loading in the absence of Scc4 increase Scc2’s association with chromosomal cohesin and reduce that of Pds5. We suggest that cohesin switches between two states: one with Pds5 bound that is unable to hydrolyze ATP efficiently but is capable of release from chromosomes and another in which Scc2 replaces Pds5 and stimulates ATP hydrolysis necessary for loading and translocation from loading sites

Original language	English
Pages (from-to)	1134-1148.e7
Number of pages	23
Journal	Molecular Cell
Volume	70
Issue number	6
Early online date	21 Jun 2018
DOIs	https://doi.org/10.1016/j.molcel.2018.05.022
Publication status	Published - 21 Jun 2018
Externally published	Yes

Bibliographical note

Acknowledgements
We are grateful to Adele Marston for sharing yeast strains; Peter West for programming support; and Tatiana Wilson, Isobel Johns, and Stefanos Skylakakis
for invaluable technical assistance. We thank all members of the Nasmyth
group for valuable discussions. This work was funded by Cancer Research
UK (C573/A12386 to K.A.N.), the Wellcome Trust (107935/Z/15/Z to K.A.N.,
202062/Z/16/Z to B.H., and 202754/Z/16/Z to J.L.), the Medical Research
Council (MR/L018047/1 to K.A.N. and U105184326 to J.L.), the European
Research Council (294401 to K.A.N.), and the Welch Foundation (I-1441 to
H.Y.). H.Y. is an Investigator with the Howard Hughes Medical Institute.

Keywords

cohesin
Scc2
Pds5
Scc1
cohesion
ATPase
loading
HAWKs

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Petela-et-al-Scc2-potent-molecular-cell-vor
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Cite this

Petela, N. J., Gligoris, T. G., Metson, J., Lee, B.-G., Voulgaris, M., Hu, B., Kikuchi, S., Chapard, C., Chen, W., Rajendra, E., Srinivisan, M., Yu, H., Löwe, J., & Nasmyth, K. A. (2018). Scc2 Is a Potent Activator of Cohesin’s ATPase that Promotes Loading by Binding Scc1 without Pds5. Molecular Cell, 70(6), 1134-1148.e7. https://doi.org/10.1016/j.molcel.2018.05.022

@article{31c6d4f3f4b6455683bff0a6cd788fc0,

title = "Scc2 Is a Potent Activator of Cohesin{\textquoteright}s ATPase that Promotes Loading by Binding Scc1 without Pds5",

abstract = "Cohesin organizes DNA into chromatids, regulates enhancer-promoter interactions, and confers sister chromatid cohesion. Its association with chromosomes is regulated by hook-shaped HEAT repeat proteins that bind Scc1, namely Scc3, Pds5, and Scc2. Unlike Pds5, Scc2 is not a stable cohesin constituent but, as shown here, transiently replaces Pds5. Scc1 mutations that compromise its interaction with Scc2 adversely affect cohesin{\textquoteright}s ATPase activity and loading. Moreover, Scc2 mutations that alter how the ATPase responds to DNA abolish loading despite cohesin{\textquoteright}s initial association with loading sites. Lastly, Scc2 mutations that permit loading in the absence of Scc4 increase Scc2{\textquoteright}s association with chromosomal cohesin and reduce that of Pds5. We suggest that cohesin switches between two states: one with Pds5 bound that is unable to hydrolyze ATP efficiently but is capable of release from chromosomes and another in which Scc2 replaces Pds5 and stimulates ATP hydrolysis necessary for loading and translocation from loading sites",

keywords = "cohesin, Scc2, Pds5, Scc1, cohesion, ATPase, loading, HAWKs",

author = "Petela, {Naomi J.} and Gligoris, {Thomas G.} and Jean Metson and Byung-Gil Lee and Menelaos Voulgaris and Bin Hu and Sotaro Kikuchi and Christophe Chapard and Wentao Chen and Eeson Rajendra and Madhusudhan Srinivisan and Hongtao Yu and Jan L{\"o}we and Nasmyth, {Kim A.}",

note = "Acknowledgements We are grateful to Adele Marston for sharing yeast strains; Peter West for programming support; and Tatiana Wilson, Isobel Johns, and Stefanos Skylakakis for invaluable technical assistance. We thank all members of the Nasmyth group for valuable discussions. This work was funded by Cancer Research UK (C573/A12386 to K.A.N.), the Wellcome Trust (107935/Z/15/Z to K.A.N., 202062/Z/16/Z to B.H., and 202754/Z/16/Z to J.L.), the Medical Research Council (MR/L018047/1 to K.A.N. and U105184326 to J.L.), the European Research Council (294401 to K.A.N.), and the Welch Foundation (I-1441 to H.Y.). H.Y. is an Investigator with the Howard Hughes Medical Institute.",

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AU - Petela, Naomi J.

AU - Gligoris, Thomas G.

AU - Metson, Jean

AU - Lee, Byung-Gil

AU - Voulgaris, Menelaos

AU - Hu, Bin

AU - Kikuchi, Sotaro

AU - Chapard, Christophe

AU - Chen, Wentao

AU - Rajendra, Eeson

AU - Srinivisan, Madhusudhan

AU - Yu, Hongtao

AU - Löwe, Jan

AU - Nasmyth, Kim A.

N1 - Acknowledgements We are grateful to Adele Marston for sharing yeast strains; Peter West for programming support; and Tatiana Wilson, Isobel Johns, and Stefanos Skylakakis for invaluable technical assistance. We thank all members of the Nasmyth group for valuable discussions. This work was funded by Cancer Research UK (C573/A12386 to K.A.N.), the Wellcome Trust (107935/Z/15/Z to K.A.N., 202062/Z/16/Z to B.H., and 202754/Z/16/Z to J.L.), the Medical Research Council (MR/L018047/1 to K.A.N. and U105184326 to J.L.), the European Research Council (294401 to K.A.N.), and the Welch Foundation (I-1441 to H.Y.). H.Y. is an Investigator with the Howard Hughes Medical Institute.

PY - 2018/6/21

Y1 - 2018/6/21

N2 - Cohesin organizes DNA into chromatids, regulates enhancer-promoter interactions, and confers sister chromatid cohesion. Its association with chromosomes is regulated by hook-shaped HEAT repeat proteins that bind Scc1, namely Scc3, Pds5, and Scc2. Unlike Pds5, Scc2 is not a stable cohesin constituent but, as shown here, transiently replaces Pds5. Scc1 mutations that compromise its interaction with Scc2 adversely affect cohesin’s ATPase activity and loading. Moreover, Scc2 mutations that alter how the ATPase responds to DNA abolish loading despite cohesin’s initial association with loading sites. Lastly, Scc2 mutations that permit loading in the absence of Scc4 increase Scc2’s association with chromosomal cohesin and reduce that of Pds5. We suggest that cohesin switches between two states: one with Pds5 bound that is unable to hydrolyze ATP efficiently but is capable of release from chromosomes and another in which Scc2 replaces Pds5 and stimulates ATP hydrolysis necessary for loading and translocation from loading sites

AB - Cohesin organizes DNA into chromatids, regulates enhancer-promoter interactions, and confers sister chromatid cohesion. Its association with chromosomes is regulated by hook-shaped HEAT repeat proteins that bind Scc1, namely Scc3, Pds5, and Scc2. Unlike Pds5, Scc2 is not a stable cohesin constituent but, as shown here, transiently replaces Pds5. Scc1 mutations that compromise its interaction with Scc2 adversely affect cohesin’s ATPase activity and loading. Moreover, Scc2 mutations that alter how the ATPase responds to DNA abolish loading despite cohesin’s initial association with loading sites. Lastly, Scc2 mutations that permit loading in the absence of Scc4 increase Scc2’s association with chromosomal cohesin and reduce that of Pds5. We suggest that cohesin switches between two states: one with Pds5 bound that is unable to hydrolyze ATP efficiently but is capable of release from chromosomes and another in which Scc2 replaces Pds5 and stimulates ATP hydrolysis necessary for loading and translocation from loading sites

KW - cohesin

KW - Scc2

KW - Pds5

KW - Scc1

KW - cohesion

KW - ATPase

KW - loading

KW - HAWKs

UR - http://europepmc.org/abstract/med/29932904

U2 - 10.1016/j.molcel.2018.05.022

DO - 10.1016/j.molcel.2018.05.022

M3 - Article

C2 - 29932904

SN - 1097-2765

VL - 70

SP - 1134-1148.e7

JO - Molecular Cell

JF - Molecular Cell

IS - 6

ER -

Scc2 Is a Potent Activator of Cohesin’s ATPase that Promotes Loading by Binding Scc1 without Pds5

Abstract

Bibliographical note

Keywords

UN SDGs

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Bin Hu

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Scc2 Is a Potent Activator of Cohesin’s ATPase that Promotes Loading by Binding Scc1 without Pds5

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Profiles

Bin Hu

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