TIAR marks nuclear G2/M transition granules and restricts CDK 1 activity under replication stress

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.