Multiple signaling kinases target Mrc1 to prevent genomic instability triggered by transcription-replication conflicts

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  • dc.contributor.author Duch, Albaca
  • dc.contributor.author Canal de Torres, Berta, 1988-ca
  • dc.contributor.author Barroso, Sonia I.ca
  • dc.contributor.author García Rubio, María Luisaca
  • dc.contributor.author Seisenbacher, Gerhardca
  • dc.contributor.author Aguilera, Andrésca
  • dc.contributor.author Nadal Clanchet, Eulàlia deca
  • dc.contributor.author Posas Garriga, Francescca
  • dc.date.accessioned 2018-04-20T07:17:17Z
  • dc.date.available 2018-04-20T07:17:17Z
  • dc.date.issued 2018
  • dc.description.abstract Conflicts 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.
  • dc.description.sponsorship The study was supported by grants from the Spanish Ministry of Economy and Competitiveness (BFU2015-64437-P and FEDER, BFU2014-52125-REDT, and BFU2014-51672-REDC to F.P.; BFU2014-52333-P and FEDER to E.N.; and BFU2013-42918 and FEDER to A.A.), the Andalusian Government (P12-BIO-1238), ERC2014-ADG669898 TARLOOP, and Worldwide Cancer Research 15-0098 to A.A. and the Catalan Government (2014 SGR 599), and the Fundación Botín, by Banco Santander through its Santander Universities Global Division to F.P. F.P. and E.d.N. are recipients of an ICREA Acadèmia (Generalitat de Catalunya).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Duch 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-x
  • dc.identifier.doi http://dx.doi.org/10.1038/s41467-017-02756-x
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/34422
  • dc.language.iso eng
  • dc.publisher Nature Publishing Groupca
  • dc.relation.ispartof Nature communications. 2018 Dec; 9(1): 379
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/669898
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-64437-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-52125-REDT
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-51672-REDC
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-52333-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2013-42918
  • dc.rights © 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/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Checkpoints
  • dc.subject.keyword Stress signalling
  • dc.title Multiple signaling kinases target Mrc1 to prevent genomic instability triggered by transcription-replication conflictsca
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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