Regulation of Claspin by the p38 stress-activated protein kinase protects cells from DNA damage

Stress-activated protein kinases (SAPKs) enhance survival in response to environmental changes. In yeast, the Hog1 SAPK and Mrc1, a protein required for DNA replication, define a safeguard mechanism that allows eukaryotic cells to prevent genomic instability upon stress during S-phase. Here we show...

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Authors: Ulsamer, Arnau, Martínez Limón, Adrián, Bader, Sina, Rodríguez-Acebes, Sara, Freire, Raimundo, Méndez, Juan, Nadal Clanchet, Eulàlia de, Posas Garriga, Francesc
Format: article
Status:Published version
Publication Date:2022
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/54827
Online Access:http://hdl.handle.net/10230/54827
http://dx.doi.org/10.1016/j.celrep.2022.111375
Access Level:Open access
Keyword:CP: Molecular biology
Claspin
DNA damage
S-phase
SAPK
Cell cycle
Cisplatin
Osmostress
p38
Stress
Transcription-replication conflicts
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network_acronym_str ES
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spelling Regulation of Claspin by the p38 stress-activated protein kinase protects cells from DNA damageUlsamer, ArnauMartínez Limón, AdriánBader, SinaRodríguez-Acebes, SaraFreire, RaimundoMéndez, JuanNadal Clanchet, Eulàlia dePosas Garriga, FrancescCP: Molecular biologyClaspinDNA damageS-phaseSAPKCell cycleCisplatinOsmostressp38StressTranscription-replication conflictsStress-activated protein kinases (SAPKs) enhance survival in response to environmental changes. In yeast, the Hog1 SAPK and Mrc1, a protein required for DNA replication, define a safeguard mechanism that allows eukaryotic cells to prevent genomic instability upon stress during S-phase. Here we show that, in mammals, the p38 SAPK and Claspin-the functional homolog of Mrc1-protect cells from DNA damage upon osmostress during S-phase. We demonstrate that p38 phosphorylates Claspin and either the mutation of the p38-phosphorylation sites in Claspin or p38 inhibition suppresses the protective role of Claspin on DNA damage. In addition, wild-type Claspin but not the p38-unphosphorylatable mutant has a protective effect on cell survival in response to cisplatin treatment. These findings reveal a role of Claspin in response to chemotherapeutic drugs. Thus, this pathway protects S-phase integrity from different insults and it is conserved from yeast to mammals.This work was supported by grants from the Spanish Ministry of Economy and Competitiveness ( PID2016-80402-R to J.M., BFU2017-85152-P to E.N., PGC2018-094136-B-I00 and FEDER to F.P., PID2021-124723NB-C21 and PID2021-124723NB-C22 to F.P. and E.N., and RED2018-102372-T to F.P., J.M., and R.F.), the Catalan Government ( 2017 SGR 799 ) and the Unidad de Excelencia Maria de Maeztu ( MDM-2014-0370 to the UPF). F.P. and E.N. are recipients of an ICREA Acadèmia (Catalan Government). We gratefully acknowledge institutional funding from the Spanish Ministry of Economy, Industry, and Competitiveness ( MINECO ) through the Centers of Excellence Severo Ochoa Award, and from the CERCA Program of the Catalan Government .Elsevier202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/54827http://dx.doi.org/10.1016/j.celrep.2022.111375reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésCell Rep. 2022 Sep 20;40(12):111375info:eu-repo/grantAgreement/ES/1PE/PID2016-80402-Rinfo:eu-repo/grantAgreement/ES/2PE/BFU2017-85152-Pinfo:eu-repo/grantAgreement/ES/2PE/PGC2018-094136-B-I00info:eu-repo/grantAgreement/ES/3PE/PID2021-124723NB-C21info:eu-repo/grantAgreement/ES/3PE/PID2021-124723NB-C22info:eu-repo/grantAgreement/ES/2PE/RED2018-102372-T© 2022 The Authors. The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/548272026-05-29T05:05:01Z
dc.title.none.fl_str_mv Regulation of Claspin by the p38 stress-activated protein kinase protects cells from DNA damage
title Regulation of Claspin by the p38 stress-activated protein kinase protects cells from DNA damage
spellingShingle Regulation of Claspin by the p38 stress-activated protein kinase protects cells from DNA damage
Ulsamer, Arnau
CP: Molecular biology
Claspin
DNA damage
S-phase
SAPK
Cell cycle
Cisplatin
Osmostress
p38
Stress
Transcription-replication conflicts
title_short Regulation of Claspin by the p38 stress-activated protein kinase protects cells from DNA damage
title_full Regulation of Claspin by the p38 stress-activated protein kinase protects cells from DNA damage
title_fullStr Regulation of Claspin by the p38 stress-activated protein kinase protects cells from DNA damage
title_full_unstemmed Regulation of Claspin by the p38 stress-activated protein kinase protects cells from DNA damage
title_sort Regulation of Claspin by the p38 stress-activated protein kinase protects cells from DNA damage
dc.creator.none.fl_str_mv Ulsamer, Arnau
Martínez Limón, Adrián
Bader, Sina
Rodríguez-Acebes, Sara
Freire, Raimundo
Méndez, Juan
Nadal Clanchet, Eulàlia de
Posas Garriga, Francesc
author Ulsamer, Arnau
author_facet Ulsamer, Arnau
Martínez Limón, Adrián
Bader, Sina
Rodríguez-Acebes, Sara
Freire, Raimundo
Méndez, Juan
Nadal Clanchet, Eulàlia de
Posas Garriga, Francesc
author_role author
author2 Martínez Limón, Adrián
Bader, Sina
Rodríguez-Acebes, Sara
Freire, Raimundo
Méndez, Juan
Nadal Clanchet, Eulàlia de
Posas Garriga, Francesc
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CP: Molecular biology
Claspin
DNA damage
S-phase
SAPK
Cell cycle
Cisplatin
Osmostress
p38
Stress
Transcription-replication conflicts
topic CP: Molecular biology
Claspin
DNA damage
S-phase
SAPK
Cell cycle
Cisplatin
Osmostress
p38
Stress
Transcription-replication conflicts
description Stress-activated protein kinases (SAPKs) enhance survival in response to environmental changes. In yeast, the Hog1 SAPK and Mrc1, a protein required for DNA replication, define a safeguard mechanism that allows eukaryotic cells to prevent genomic instability upon stress during S-phase. Here we show that, in mammals, the p38 SAPK and Claspin-the functional homolog of Mrc1-protect cells from DNA damage upon osmostress during S-phase. We demonstrate that p38 phosphorylates Claspin and either the mutation of the p38-phosphorylation sites in Claspin or p38 inhibition suppresses the protective role of Claspin on DNA damage. In addition, wild-type Claspin but not the p38-unphosphorylatable mutant has a protective effect on cell survival in response to cisplatin treatment. These findings reveal a role of Claspin in response to chemotherapeutic drugs. Thus, this pathway protects S-phase integrity from different insults and it is conserved from yeast to mammals.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/54827
http://dx.doi.org/10.1016/j.celrep.2022.111375
url http://hdl.handle.net/10230/54827
http://dx.doi.org/10.1016/j.celrep.2022.111375
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Cell Rep. 2022 Sep 20;40(12):111375
info:eu-repo/grantAgreement/ES/1PE/PID2016-80402-R
info:eu-repo/grantAgreement/ES/2PE/BFU2017-85152-P
info:eu-repo/grantAgreement/ES/2PE/PGC2018-094136-B-I00
info:eu-repo/grantAgreement/ES/3PE/PID2021-124723NB-C21
info:eu-repo/grantAgreement/ES/3PE/PID2021-124723NB-C22
info:eu-repo/grantAgreement/ES/2PE/RED2018-102372-T
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,198674

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