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

Ulsamer, Arnau; Martínez Limón, Adrián; Bader, Sina; Rodríguez-Acebes, Sara; Freire, Raimundo; Méndez, Juan; Nadal Clanchet, Eulàlia de; Posas Garriga, Francesc

doi:http://dx.doi.org/10.1016/j.celrep.2022.111375

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

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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

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.