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dc.contributor.authorLafarga, Vanesa 
dc.contributor.authorSung, Hsu-Min
dc.contributor.authorHaneke, Katharina
dc.contributor.authorRoessig, Lea
dc.contributor.authorPauleau, Anne-Laure
dc.contributor.authorBruer, Marius
dc.contributor.authorRodriguez-Acebes, Sara 
dc.contributor.authorLopez-Contreras, Andres J
dc.contributor.authorGruss, Oliver J
dc.contributor.authorErhardt, Sylvia
dc.contributor.authorMendez, Juan 
dc.contributor.authorFernandez-Capetillo, Oscar 
dc.contributor.authorStoecklin, Georg
dc.identifier.citationEMBO Rep. 2019;20(1). pii: e46224.es_ES
dc.description.abstractThe G2/M checkpoint coordinates DNA replication with mitosis and thereby prevents chromosome segregation in the presence of unreplicated or damaged DNA Here, we show that the RNA-binding protein TIAR is essential for the G2/M checkpoint and that TIAR accumulates in nuclear foci in late G2 and prophase in cells suffering from replication stress. These foci, which we named G2/M transition granules (GMGs), occur at low levels in normally cycling cells and are strongly induced by replication stress. In addition to replication stress response proteins, GMGs contain factors involved in RNA metabolism as well as CDK1. Depletion of TIAR accelerates mitotic entry and leads to chromosomal instability in response to replication stress, in a manner that can be alleviated by the concomitant depletion of Cdc25B or inhibition of CDK1. Since TIAR retains CDK1 in GMGs and attenuates CDK1 activity, we propose that the assembly of GMGs may represent a so far unrecognized mechanism that contributes to the activation of the G2/M checkpoint in mammalian cells.es_ES
dc.description.sponsorshipWe would like to thank Nancy Kedersha and Paul Anderson (both Harvard Medical School, Boston, USA) for sharing plasmids and thoughtful comments on the manuscript, Thomas Hofmann (DKFZ, Heidelberg) for sharing ideas and reagents, Jan Ellenberg (EMBL Heidelberg, Germany) for sharing the HeLa‐H2B/tub cell line, Iain Mattaj (EMBL Heidelberg, Germany) for sharing the anti‐Sm (Y12) antibody, Angus Lamond (University of Dundee, UK) for sharing the anti‐Coilin antibody, Ingrid Hoffmann (DKFZ Heidelberg, Germany) for sharing the mCherry‐CDK1 plasmid, as well as Guillermo de Carcer (CNIO), Ana Losada (CNIO), and Brian Luke (ZMBH, Heidelberg) for thoughtful comments and critical reading of the manuscript. We also thank Holger Lorenz and Diego Megias from the ZMBH and CNIO imaging core facilities for assistance with microscopy and Monika Langloz from the ZMBH FACS facility for help with flow cytometry. We are grateful to Kathrin Bajak for experimental contributions. This work was supported by a Marie‐Curie Intra‐European Fellowship (mirnaAGOddr, grant Nr. 300384) to VL, doctoral fellowships from the Heidelberg Biosciences International Graduate School to H‐MS and MB, grant Nr. 111219 from the Deutsche Krebshilfe to VL and GS, and grant SFB 1036/TP07 from the Deutsche Forschungsgemeinschaft to GS.es_ES
dc.publisherWiley es_ES
dc.subjectG2/M checkpointes_ES
dc.subjectRNA‐binding proteines_ES
dc.subjectcell cyclees_ES
dc.titleTIAR marks nuclear G2/M transition granules and restricts CDK1 activity under replication stresses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.contributor.funderGerman Cancer Aid 
dc.contributor.funderDeutsche Forschungsgemeinschaft (Alemania) 
dc.identifier.journalEMBO reportses_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Inestabilidad Genómicaes_ES
dc.rights.accessRightsopen accesses_ES

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