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TIAR marks nuclear G2/M transition granules and restricts CDK 1 activity under replication stress
Author(s) -
Lafarga Vanesa,
Sung HsuMin,
Haneke Katharina,
Roessig Lea,
Pauleau AnneLaure,
Bruer Marius,
RodriguezAcebes Sara,
LopezContreras Andres J,
Gruss Oliver J,
Erhardt Sylvia,
Mendez Juan,
FernandezCapetillo Oscar,
Stoecklin Georg
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201846224
Subject(s) - german , biomedicine , biology , genetics , history , archaeology
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 ( GMG s), occur at low levels in normally cycling cells and are strongly induced by replication stress. In addition to replication stress response proteins, GMG s contain factors involved in RNA metabolism as well as CDK 1. 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 CDK 1. Since TIAR retains CDK 1 in GMG s and attenuates CDK 1 activity, we propose that the assembly of GMG s may represent a so far unrecognized mechanism that contributes to the activation of the G2/M checkpoint in mammalian cells.