Residual Cdk1/2 activity after DNA damage promotes senescence

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F17%3A00486699" target="_blank" >RIV/68378050:_____/17:00486699 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1111/acel.12588" target="_blank" >http://dx.doi.org/10.1111/acel.12588</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/acel.12588" target="_blank" >10.1111/acel.12588</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Residual Cdk1/2 activity after DNA damage promotes senescence

Popis výsledku v původním jazyce

In response to DNA damage, a cell can be forced to permanently exit the cell cycle and become senescent. Senescence provides an early barrier against tumor development by preventing proliferation of cells with damaged DNA. By studying single cells, we show that Cdk activity persists after DNA damage until terminal cell cycle exit. This low level of Cdk activity not only allows cell cycle progression, but also promotes cell cycle exit at a decision point in G2 phase. We find that residual Cdk1/2 activity is required for efficient p21 production, allowing for nuclear sequestration of Cyclin B1, subsequent APC/C-Cdh1-dependent degradation of mitotic inducers and induction of senescence. We suggest that the same activity that triggers mitosis in an unperturbed cell cycle enforces senescence in the presence of DNA damage, ensuring a robust response when most needed.

Název v anglickém jazyce

Residual Cdk1/2 activity after DNA damage promotes senescence

Popis výsledku anglicky

In response to DNA damage, a cell can be forced to permanently exit the cell cycle and become senescent. Senescence provides an early barrier against tumor development by preventing proliferation of cells with damaged DNA. By studying single cells, we show that Cdk activity persists after DNA damage until terminal cell cycle exit. This low level of Cdk activity not only allows cell cycle progression, but also promotes cell cycle exit at a decision point in G2 phase. We find that residual Cdk1/2 activity is required for efficient p21 production, allowing for nuclear sequestration of Cyclin B1, subsequent APC/C-Cdh1-dependent degradation of mitotic inducers and induction of senescence. We suggest that the same activity that triggers mitosis in an unperturbed cell cycle enforces senescence in the presence of DNA damage, ensuring a robust response when most needed.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular 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

AGING CELL

ISSN

1474-9726

e-ISSN

—

Svazek periodika

16

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

575-584

Kód UT WoS článku

000402426900016

EID výsledku v databázi Scopus

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