TIAR marks nuclear G2/M transition granules and restricts CDK1 activity under replication stress.

Autor: Lafarga V; German Cancer Research Center (DKFZ), Heidelberg, Germany vlafarga@cnio.es georg.stoecklin@medma.uni-heidelberg.de.; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany.; Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Sung HM; German Cancer Research Center (DKFZ), Heidelberg, Germany.; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany.; Division of Biochemistry, Center for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Haneke K; German Cancer Research Center (DKFZ), Heidelberg, Germany.; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany.; Division of Biochemistry, Center for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Roessig L; German Cancer Research Center (DKFZ), Heidelberg, Germany.; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany., Pauleau AL; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany.; Department of Cellular and Molecular Medicine, Center for Chromosome Stability and Center for Healthy Aging University of Copenhagen, Copenhagen, Denmark., Bruer M; German Cancer Research Center (DKFZ), Heidelberg, Germany.; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany.; Division of Biochemistry, Center for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Rodriguez-Acebes S; Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Lopez-Contreras AJ; Spanish National Cancer Research Centre (CNIO), Madrid, Spain.; CellNetworks Excellence Cluster, Heidelberg University, Heidelberg, Germany., Gruss OJ; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany., Erhardt S; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany.; Department of Cellular and Molecular Medicine, Center for Chromosome Stability and Center for Healthy Aging University of Copenhagen, Copenhagen, Denmark., Mendez J; Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Fernandez-Capetillo O; Spanish National Cancer Research Centre (CNIO), Madrid, Spain.; Science for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden., Stoecklin G; German Cancer Research Center (DKFZ), Heidelberg, Germany vlafarga@cnio.es georg.stoecklin@medma.uni-heidelberg.de.; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany.; Division of Biochemistry, Center for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Jazyk: angličtina
Zdroj: EMBO reports [EMBO Rep] 2019 Jan; Vol. 20 (1). Date of Electronic Publication: 2018 Dec 11.
DOI: 10.15252/embr.201846224
Abstrakt: The 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.
(© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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