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oai:repisalud.isciii.es:20.500.12105/75522024-11-29T23:05:41Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Lafarga, Vanesa author Sung, Hsu-Min author Haneke, Katharina author Roessig, Lea author Pauleau, Anne-Laure author Bruer, Marius author Rodriguez-Acebes, Sara author Lopez-Contreras, Andres J author Gruss, Oliver J author Erhardt, Sylvia author Mendez, Juan author Fernandez-Capetillo, Oscar author Stoecklin, Georg author 2019-01 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. EMBO Rep. 2019;20(1). pii: e46224. 10.15252/embr.201846224 1469-3178 1469-221X EMBO reports 30538118 http://hdl.handle.net/20.500.12105/7552 TIAR CDK1 G2/M checkpoint RNA‐binding protein cell cycle TIAR marks nuclear G2/M transition granules and restricts CDK1 activity under replication stress