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

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• dc.contributor.author Ulsamer, Arnau
• dc.contributor.author Martínez Limón, Adrián
• dc.contributor.author Bader, Sina
• dc.contributor.author Rodríguez-Acebes, Sara
• dc.contributor.author Freire, Raimundo
• dc.contributor.author Méndez, Juan
• dc.contributor.author Nadal Clanchet, Eulàlia de
• dc.contributor.author Posas Garriga, Francesc
• dc.date.accessioned 2022-11-14T07:13:12Z
• dc.date.available 2022-11-14T07:13:12Z
• dc.date.issued 2022
• dc.description.abstract 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.
• dc.description.sponsorship 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 .
• dc.format.mimetype application/pdf
• dc.identifier.citation Ulsamer A, Martínez-Limón A, Bader S, Rodríguez-Acebes S, Freire R, Méndez J, de Nadal E, Posas F. Regulation of Claspin by the p38 stress-activated protein kinase protects cells from DNA damage. Cell Rep. 2022 Sep 20;40(12):111375. DOI: 10.1016/j.celrep.2022.111375
• dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2022.111375
• dc.identifier.issn 2211-1247
• dc.identifier.uri http://hdl.handle.net/10230/54827
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Cell Rep. 2022 Sep 20;40(12):111375
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/PID2016-80402-R
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-85152-P
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-094136-B-I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-124723NB-C21
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-124723NB-C22
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RED2018-102372-T
• dc.rights © 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/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword CP: Molecular biology
• dc.subject.keyword Claspin
• dc.subject.keyword DNA damage
• dc.subject.keyword S-phase
• dc.subject.keyword SAPK
• dc.subject.keyword Cell cycle
• dc.subject.keyword Cisplatin
• dc.subject.keyword Osmostress
• dc.subject.keyword p38
• dc.subject.keyword Stress
• dc.subject.keyword Transcription-replication conflicts
• dc.title Regulation of Claspin by the p38 stress-activated protein kinase protects cells from DNA damage
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion