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oai:recercat.cat:2445/2206082025-12-04T19:32:11Zcom_2072_1057col_2072_478908col_2072_478917

Regulation of Claspin by the p38 stress-activated protein kinase protects cells from DNA damage Ulsamer, Arnau Martínez Limón, Adrián Bader, S Rodríguez Acebes, Sara Freire, Raimundo Méndez, Juan Nadal Clanchet, Eulàlia de Posas, Francesc ADN Estrès (Fisiologia) Cicle cel·lular Cisplatí DNA Stress (Physiology) Cell cycle Cisplatin 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. 2025-04-25T09:23:57Z 2025-04-25T09:23:57Z 2022-09-20 2025-04-23T07:18:57Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 2211-1247 https://hdl.handle.net/2445/220608 6567540 36130506 eng Reproducció del document publicat a:  https://doi.org/10.1016/j.celrep.2022.111375 Cell Reports, 2022, vol. 40, num. 12 https://doi.org/10.1016/j.celrep.2022.111375 cc-by-nc-nd (c) Ulsamer, Arnau et al., 2022 http://creativecommons.org/licenses/by-nc-nd/3.0/es/ info:eu-repo/semantics/openAccess 17 p. application/pdf Elsevier Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))