TY  - JOUR
AU  - Lafarga, Vanesa
AU  - Sung, Hsu-Min
AU  - Haneke, Katharina
AU  - Roessig, Lea
AU  - Pauleau, Anne-Laure
AU  - Bruer, Marius
AU  - Rodriguez-Acebes, Sara
AU  - Lopez-Contreras, Andres J
AU  - Gruss, Oliver J
AU  - Erhardt, Sylvia
AU  - Mendez, Juan
AU  - Fernandez-Capetillo, Oscar
AU  - Stoecklin, Georg
TI  - TIAR marks nuclear G2/M transition granules and restricts CDK1 activity under replication stress.
JO  - EMBO reports
VL  - 20
IS  - 1
SN  - 1469-3178
CY  - Hoboken, NJ [u.a.]
PB  - Wiley
M1  - DKFZ-2019-00670
SP  - e46224 
PY  - 2019
N1  - DKFZ-ZMBH-Alliance
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30538118
C2  - pmc:PMC6322364
DO  - DOI:10.15252/embr.201846224
UR  - https://inrepo02.dkfz.de/record/143051
ER  -