Ubiquitin-activating enzyme UBA1 is required for cellular response to DNA damage

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F12%3A33140827" target="_blank" >RIV/61989592:15110/12:33140827 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378050:_____/12:00387884

Výsledek na webu

<a href="http://dx.doi.org/10.4161/cc.19978" target="_blank" >http://dx.doi.org/10.4161/cc.19978</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.4161/cc.19978" target="_blank" >10.4161/cc.19978</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Ubiquitin-activating enzyme UBA1 is required for cellular response to DNA damage

Popis výsledku v původním jazyce

The cellular DNA damage response (DDR) machinery that maintains genomic integrity and prevents severe pathologies, including cancer, is orchestrated by signaling through protein modifications. Protein ubiquitylation regulates repair of DNA double-strandbreaks (DSBs), toxic lesions caused by various metabolic as well as environmental insults such as ionizing radiation (IR). Whereas several components of the DSB-evoked ubiquitylation cascade have been identified, including RNF168 and BRCA1 ubiquitin ligases, whose genetic defects predispose to a syndrome mimicking ataxiatelangiectasia and cancer, respectively, the identity of the apical E1 enzyme involved in DDR has not been established. Here, we identify ubiquitin-activating enzyme UBA1 as the E1 enzyme required for responses to IR and replication stress in human cells. We show that siRNA-mediated knockdown of UBA1, but not of another UBA family member UBA6, impaired formation of both ubiquitin conjugates at the sites of DNA damage and

Název v anglickém jazyce

Ubiquitin-activating enzyme UBA1 is required for cellular response to DNA damage

Popis výsledku anglicky

The cellular DNA damage response (DDR) machinery that maintains genomic integrity and prevents severe pathologies, including cancer, is orchestrated by signaling through protein modifications. Protein ubiquitylation regulates repair of DNA double-strandbreaks (DSBs), toxic lesions caused by various metabolic as well as environmental insults such as ionizing radiation (IR). Whereas several components of the DSB-evoked ubiquitylation cascade have been identified, including RNF168 and BRCA1 ubiquitin ligases, whose genetic defects predispose to a syndrome mimicking ataxiatelangiectasia and cancer, respectively, the identity of the apical E1 enzyme involved in DDR has not been established. Here, we identify ubiquitin-activating enzyme UBA1 as the E1 enzyme required for responses to IR and replication stress in human cells. We show that siRNA-mediated knockdown of UBA1, but not of another UBA family member UBA6, impaired formation of both ubiquitin conjugates at the sites of DNA damage and

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

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2012

Kód důvěrnosti údajů

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

Název periodika

CELL CYCLE

ISSN

1538-4101

e-ISSN

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Svazek periodika

11

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

1573-1582

Kód UT WoS článku

000303162100019

EID výsledku v databázi Scopus

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