A Comprehensive Analysis of the Dynamic Response to Aphidicolin-Mediated Replication Stress Uncovers Targets for ATM and ATMIN

Abstract : The cellular response to replication stress requires the DNA-damage-responsive kinase ATM and its cofactor ATMIN; however, the roles of this signaling pathway following replication stress are unclear. To identify the functions of ATM and ATMIN in response to replication stress, we utilized both transcriptomics and quantitative mass-spectrometry-based phosphoproteomics. We found that replication stress induced by aphidicolin triggered widespread changes in both gene expression and protein phosphorylation patterns. These changes gave rise to distinct early and late replication stress responses. Furthermore, our analysis revealed previously unknown targets of ATM and ATMIN downstream of replication stress. We demonstrate ATMIN-dependent phosphorylation of H2AX and of CRMP2, a protein previously implicated in Alzheimer's disease but not in the DNA damage response. Overall, our dataset provides a comprehensive resource for discovering the cellular responses to replication stress and, potentially, associated pathologies.
Type de document :
Article dans une revue
Liste complète des métadonnées

Littérature citée [56 références]  Voir  Masquer  Télécharger

https://hal.umontpellier.fr/hal-02297707
Contributeur : Anthony Herrada <>
Soumis le : jeudi 26 septembre 2019 - 13:08:30
Dernière modification le : vendredi 27 septembre 2019 - 01:22:43

Fichier

1-s2.0-S2211124716303667-main....
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Collections

Citation

Abdelghani Mazouzi, Alexey Stukalov, André Müller, Doris Chen, Marc Wiedner, et al.. A Comprehensive Analysis of the Dynamic Response to Aphidicolin-Mediated Replication Stress Uncovers Targets for ATM and ATMIN. Cell Reports , Elsevier Inc, 2016, 15 (4), pp.893-908. ⟨10.1016/j.celrep.2016.03.077⟩. ⟨hal-02297707⟩

Partager

Métriques

Consultations de la notice

22

Téléchargements de fichiers

28