ATM/Wip1 activities at chromatin control Plk1 re-activation to determine G2 checkpoint duration

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F17%3A00483738" target="_blank" >RIV/68378050:_____/17:00483738 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/17:10369008

Výsledek na webu

<a href="http://dx.doi.org/10.15252/embj.201696082" target="_blank" >http://dx.doi.org/10.15252/embj.201696082</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.15252/embj.201696082" target="_blank" >10.15252/embj.201696082</a>

Jazyk výsledku

angličtina

Název v původním jazyce

ATM/Wip1 activities at chromatin control Plk1 re-activation to determine G2 checkpoint duration

Popis výsledku v původním jazyce

After DNA damage, the cell cycle is arrested to avoid propagation of mutations. Arrest in G2 phase is initiated by ATM-/ATR-dependent signaling that inhibits mitosis-promoting kinases such as Plk1. At the same time, Plk1 can counteract ATR-dependent signaling and is required for eventual resumption of the cell cycle. However, what determines when Plk1 activity can resume remains unclear. Here, we use FRET-based reporters to show that a global spread of ATM activity on chromatin and phosphorylation of ATM targets including KAP1 control Plk1 re-activation. These phosphorylations are rapidly counteracted by the chromatin-bound phosphatase Wip1, allowing cell cycle restart despite persistent ATM activity present at DNA lesions. Combining experimental data and mathematical modeling, we propose a model for how the minimal duration of cell cycle arrest is controlled. Our model shows how cell cycle restart can occur before completion of DNA repair and suggests a mechanism for checkpoint adaptation in human cells.

Název v anglickém jazyce

ATM/Wip1 activities at chromatin control Plk1 re-activation to determine G2 checkpoint duration

Popis výsledku anglicky

After DNA damage, the cell cycle is arrested to avoid propagation of mutations. Arrest in G2 phase is initiated by ATM-/ATR-dependent signaling that inhibits mitosis-promoting kinases such as Plk1. At the same time, Plk1 can counteract ATR-dependent signaling and is required for eventual resumption of the cell cycle. However, what determines when Plk1 activity can resume remains unclear. Here, we use FRET-based reporters to show that a global spread of ATM activity on chromatin and phosphorylation of ATM targets including KAP1 control Plk1 re-activation. These phosphorylations are rapidly counteracted by the chromatin-bound phosphatase Wip1, allowing cell cycle restart despite persistent ATM activity present at DNA lesions. Combining experimental data and mathematical modeling, we propose a model for how the minimal duration of cell cycle arrest is controlled. Our model shows how cell cycle restart can occur before completion of DNA repair and suggests a mechanism for checkpoint adaptation in human cells.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

<a href="/cs/project/GA13-18392S" target="_blank" >GA13-18392S: Dynamika buněčné odpovědi na poškození DNA</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

EMBO Journal

ISSN

0261-4189

e-ISSN

—

Svazek periodika

36

Číslo periodika v rámci svazku

14

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

16

Strana od-do

2161-2176

Kód UT WoS článku

000405478400013

EID výsledku v databázi Scopus

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