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

Result code in 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>

Alternative codes found

RIV/00216208:11310/17:10369008

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10601 - Cell biology

Project

<a href="/en/project/GA13-18392S" target="_blank" >GA13-18392S: Dynamics of DNA damage response in cells</a><br>

Continuities

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

Publication year

2017

Confidentiality

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

Name of the periodical

EMBO Journal

ISSN

0261-4189

e-ISSN

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Volume of the periodical

36

Issue of the periodical within the volume

14

Country of publishing house

GB - UNITED KINGDOM

Number of pages

16

Pages from-to

2161-2176

UT code for WoS article

000405478400013

EID of the result in the Scopus database

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