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

Abdelghani Mazouzi | Zendy; Alexey Stukalov | Zendy; André C. Müller | Zendy; Doris Chen | Zendy; Marc Wiedner | Zendy; Jana Procházková | Zendy; ShihChieh Chiang | Zendy; Michael Schuster | Zendy; Florian P. Breitwieser | Zendy; Andreas Pichlmair | Zendy; Sherif F. ElKhamisy | Zendy; Christoph Bock | Zendy; Róbert Královics | Zendy; Jacques Colinge | Zendy; Keiryn L. Bennett | Zendy; Joanna I. Loizou | Zendy

Open Access

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

Author(s) -

Abdelghani Mazouzi,

Alexey Stukalov,

André C. Müller,

Doris Chen,

Marc Wiedner,

Jana Procházková,

ShihChieh Chiang,

Michael Schuster,

Florian P. Breitwieser,

Andreas Pichlmair,

Sherif F. ElKhamisy,

Christoph Bock,

Róbert Královics,

Jacques Colinge,

Keiryn L. Bennett,

Joanna I. Loizou

Publication year - 2016

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2016.03.077

Subject(s) - aphidicolin , dna damage , replication timing , dna replication , phosphoproteomics , biology , transcriptome , microbiology and biotechnology , replication (statistics) , phosphorylation , protein phosphorylation , gene , genetics , dna , gene expression , protein kinase a , virology

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.

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