Immortalised breast epithelia survive prolonged DNA replication stress and return to cycle from a senescent-like state

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F14%3A33151023" target="_blank" >RIV/61989592:15110/14:33151023 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1038/cddis.2014.315" target="_blank" >http://dx.doi.org/10.1038/cddis.2014.315</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/cddis.2014.315" target="_blank" >10.1038/cddis.2014.315</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Immortalised breast epithelia survive prolonged DNA replication stress and return to cycle from a senescent-like state

Popis výsledku v původním jazyce

Mammalian cells have mechanisms to counteract the effects of metabolic and exogenous stresses, many of that would be mutagenic if ignored. Damage arising during DNA replication is a major source of mutagenesis. The extent of damage dictates whether cellsundergo transient cell cycle arrest and damage repair, senescence or apoptosis. Existing dogma defines these alternative fates as distinct choices. Here we show that immortalised breast epithelial cells are able to survive prolonged S phase arrest and subsequently re-enter cycle after many days of being in an arrested, senescence-like state. Prolonged cell cycle inhibition in fibroblasts induced DNA damage response and cell death. However, in immortalised breast epithelia, efficient S phase arrest minimised chromosome damage and protected sufficient chromatin-bound replication licensing complexes to allow cell cycle re-entry. We propose that our observation could have implications for the design of drug therapies for breast cancer.

Název v anglickém jazyce

Immortalised breast epithelia survive prolonged DNA replication stress and return to cycle from a senescent-like state

Popis výsledku anglicky

Mammalian cells have mechanisms to counteract the effects of metabolic and exogenous stresses, many of that would be mutagenic if ignored. Damage arising during DNA replication is a major source of mutagenesis. The extent of damage dictates whether cellsundergo transient cell cycle arrest and damage repair, senescence or apoptosis. Existing dogma defines these alternative fates as distinct choices. Here we show that immortalised breast epithelial cells are able to survive prolonged S phase arrest and subsequently re-enter cycle after many days of being in an arrested, senescence-like state. Prolonged cell cycle inhibition in fibroblasts induced DNA damage response and cell death. However, in immortalised breast epithelia, efficient S phase arrest minimised chromosome damage and protected sufficient chromatin-bound replication licensing complexes to allow cell cycle re-entry. We propose that our observation could have implications for the design of drug therapies for breast cancer.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

<a href="/cs/project/ED0030%2F01%2F01" target="_blank" >ED0030/01/01: Biomedicína pro regionální rozvoj a lidské zdroje</a><br>

Návaznosti

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

Rok uplatnění

2014

Kód důvěrnosti údajů

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

Název periodika

CELL DEATH & DISEASE

ISSN

2041-4889

e-ISSN

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Svazek periodika

5

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

"e1351-1"-"e1351-13"

Kód UT WoS článku

000341639300042

EID výsledku v databázi Scopus

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