Ulsamer, ArnauMartínez Limón, AdriánBader, SinaRodríguez-Acebes, SaraFreire, RaimundoMéndez, JuanNadal Clanchet, Eulàlia dePosas Garriga, Francesc2022-11-142022-11-142022Ulsamer 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.2022.1113752211-1247http://hdl.handle.net/10230/54827Stress-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.application/pdfeng© 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/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.celrep.2022.111375CP: Molecular biologyClaspinDNA damageS-phaseSAPKCell cycleCisplatinOsmostressp38StressTranscription-replication conflictsinfo:eu-repo/semantics/openAccess