Duch, AlbaCanal de Torres, Berta, 1988-Barroso, Sonia I.García Rubio, María LuisaSeisenbacher, GerhardAguilera, AndrésNadal Clanchet, Eulàlia dePosas Garriga, Francesc2018-04-202018-04-202018Duch A, Canal B, Barroso SI, García-Rubio M, Seisenbacher G, Aguilera A et al. Multiple signaling kinases target Mrc1 to prevent genomic instability triggered by transcription-replication conflicts. Nat Commun 2018 Dec;9(1):379. DOI: 10.1038/s41467-017-02756-x2041-1723http://hdl.handle.net/10230/34422Conflicts between replication and transcription machineries represent a major source of genomic instability and cells have evolved strategies to prevent such conflicts. However, little is known regarding how cells cope with sudden increases of transcription while replicating. Here, we report the existence of a general mechanism for the protection of genomic integrity upon transcriptional outbursts in S phase that is mediated by Mrc1. The N-terminal phosphorylation of Mrc1 blocked replication and prevented transcription-associated recombination (TAR) and genomic instability during stress-induced gene expression in S phase. An unbiased kinome screening identified several kinases that phosphorylate Mrc1 at the N terminus upon different environmental stresses. Mrc1 function was not restricted to environmental cues but was also required when unscheduled transcription was triggered by low fitness states such as genomic instability or slow growth. Our data indicate that Mrc1 integrates multiple signals, thereby defining a general safeguard mechanism to protect genomic integrity upon transcriptional outbursts.application/pdfeng© The Author(s) 2018. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-017-02756-xCheckpointsStress signallinginfo:eu-repo/semantics/openAccess