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

Vanesa Lafarga; Hsu-Min Sung; Katharina Haneke; Lea Roessig; Anne-Laure Pauleau; Marius Bruer; Sara Rodriguez-Acebes; Andres J Lopez-Contreras; Oliver J Gruss; Sylvia Erhardt; Juan Mendez; Oscar Fernandez-Capetillo; Georg Stoecklin

doi:10.15252/embr.201846224

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

Vanesa Lafarga, Hsu-Min Sung, Katharina Haneke, Lea Roessig, Anne-Laure Pauleau, Marius Bruer, Sara Rodriguez-Acebes, Andres J Lopez-Contreras, Oliver J Gruss, Sylvia Erhardt, Juan Mendez, Oscar Fernandez-Capetillo, Georg Stoecklin

Molecular Aging Program

6 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	EMBO Reports
Vol/bind	20
Udgave nummer	1
ISSN	1469-221X
DOI	https://doi.org/10.15252/embr.201846224
Status	Udgivet - jan. 2019

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10.15252/embr.201846224Licens: CC BY

http://europepmc.org/articles/pmc6322364?pdf=renderLicens: CC BY

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title = "TIAR marks nuclear G2/M transition granules and restricts CDK1 activity under replication stress",

abstract = "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.",

author = "Vanesa Lafarga and Hsu-Min Sung and Katharina Haneke and Lea Roessig and Anne-Laure Pauleau and Marius Bruer and Sara Rodriguez-Acebes and Lopez-Contreras, {Andres J} and Gruss, {Oliver J} and Sylvia Erhardt and Juan Mendez and Oscar Fernandez-Capetillo and Georg Stoecklin",

note = "{\textcopyright} 2018 The Authors. Published under the terms of the CC BY 4.0 license.",

year = "2019",

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doi = "10.15252/embr.201846224",

language = "English",

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T1 - TIAR marks nuclear G2/M transition granules and restricts CDK1 activity under replication stress

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

PY - 2019/1

Y1 - 2019/1

N2 - 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.

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.

U2 - 10.15252/embr.201846224

DO - 10.15252/embr.201846224

M3 - Journal article

C2 - 30538118

SN - 1469-221X

VL - 20

JO - E M B O Reports

JF - E M B O Reports

IS - 1

ER -

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

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