Cargando…

SET binding to Sgo1 inhibits Sgo1–cohesin interactions and promotes chromosome segregation

At anaphase onset, Sgo1 function of cohesion protection must be disabled to allow timely chromosome segregation, but how this is achieved is not fully understood. Here, we show that SET, a known PP2A inhibitor, directly binds to a domain in Sgo1 in close proximity to the cohesin-binding motif. The S...

Descripción completa

Detalles Bibliográficos
Autores principales: Qu, Qianhui, Zhang, Qian, Yang, Lu, Chen, Yujue, Liu, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683731/
https://www.ncbi.nlm.nih.gov/pubmed/31227592
http://dx.doi.org/10.1083/jcb.201810096
_version_ 1783442144007028736
author Qu, Qianhui
Zhang, Qian
Yang, Lu
Chen, Yujue
Liu, Hong
author_facet Qu, Qianhui
Zhang, Qian
Yang, Lu
Chen, Yujue
Liu, Hong
author_sort Qu, Qianhui
collection PubMed
description At anaphase onset, Sgo1 function of cohesion protection must be disabled to allow timely chromosome segregation, but how this is achieved is not fully understood. Here, we show that SET, a known PP2A inhibitor, directly binds to a domain in Sgo1 in close proximity to the cohesin-binding motif. The Sgo1–cohesin binding can be disrupted by SET in a dose-dependent manner in vitro as well as by SET overexpression in cells, suggesting that SET is also an inhibitor to the Sgo1–cohesin binding. Furthermore, the SET binding–deficient Sgo1 mutant fully supports centromeric cohesion protection but delays chromosome segregation, suggesting that the SET–Sgo1 binding is required for timely chromosome segregation. Moreover, overexpression of SET WT, not the Sgo1 binding–deficient mutant, exacerbates the occurrence of cohesion fatigue in MG132-arrested cells. Conversely, SET depletion delays it. Thus, we propose that a major function of SET during mitosis is to disrupt the Sgo1–cohesin interaction, thereby promoting centromeric cohesion de-protection and timely chromosome segregation at anaphase onset.
format Online
Article
Text
id pubmed-6683731
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-66837312020-02-05 SET binding to Sgo1 inhibits Sgo1–cohesin interactions and promotes chromosome segregation Qu, Qianhui Zhang, Qian Yang, Lu Chen, Yujue Liu, Hong J Cell Biol Research Articles At anaphase onset, Sgo1 function of cohesion protection must be disabled to allow timely chromosome segregation, but how this is achieved is not fully understood. Here, we show that SET, a known PP2A inhibitor, directly binds to a domain in Sgo1 in close proximity to the cohesin-binding motif. The Sgo1–cohesin binding can be disrupted by SET in a dose-dependent manner in vitro as well as by SET overexpression in cells, suggesting that SET is also an inhibitor to the Sgo1–cohesin binding. Furthermore, the SET binding–deficient Sgo1 mutant fully supports centromeric cohesion protection but delays chromosome segregation, suggesting that the SET–Sgo1 binding is required for timely chromosome segregation. Moreover, overexpression of SET WT, not the Sgo1 binding–deficient mutant, exacerbates the occurrence of cohesion fatigue in MG132-arrested cells. Conversely, SET depletion delays it. Thus, we propose that a major function of SET during mitosis is to disrupt the Sgo1–cohesin interaction, thereby promoting centromeric cohesion de-protection and timely chromosome segregation at anaphase onset. Rockefeller University Press 2019-08-05 2019-06-21 /pmc/articles/PMC6683731/ /pubmed/31227592 http://dx.doi.org/10.1083/jcb.201810096 Text en © 2019 Qu et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Qu, Qianhui
Zhang, Qian
Yang, Lu
Chen, Yujue
Liu, Hong
SET binding to Sgo1 inhibits Sgo1–cohesin interactions and promotes chromosome segregation
title SET binding to Sgo1 inhibits Sgo1–cohesin interactions and promotes chromosome segregation
title_full SET binding to Sgo1 inhibits Sgo1–cohesin interactions and promotes chromosome segregation
title_fullStr SET binding to Sgo1 inhibits Sgo1–cohesin interactions and promotes chromosome segregation
title_full_unstemmed SET binding to Sgo1 inhibits Sgo1–cohesin interactions and promotes chromosome segregation
title_short SET binding to Sgo1 inhibits Sgo1–cohesin interactions and promotes chromosome segregation
title_sort set binding to sgo1 inhibits sgo1–cohesin interactions and promotes chromosome segregation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683731/
https://www.ncbi.nlm.nih.gov/pubmed/31227592
http://dx.doi.org/10.1083/jcb.201810096
work_keys_str_mv AT quqianhui setbindingtosgo1inhibitssgo1cohesininteractionsandpromoteschromosomesegregation
AT zhangqian setbindingtosgo1inhibitssgo1cohesininteractionsandpromoteschromosomesegregation
AT yanglu setbindingtosgo1inhibitssgo1cohesininteractionsandpromoteschromosomesegregation
AT chenyujue setbindingtosgo1inhibitssgo1cohesininteractionsandpromoteschromosomesegregation
AT liuhong setbindingtosgo1inhibitssgo1cohesininteractionsandpromoteschromosomesegregation