ATR Prohibits Replication Catastrophe by Preventing Global Exhaustion of RPA

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F13%3A33145223" target="_blank" >RIV/61989592:15110/13:33145223 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.cell.2013.10.043" target="_blank" >http://dx.doi.org/10.1016/j.cell.2013.10.043</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.cell.2013.10.043" target="_blank" >10.1016/j.cell.2013.10.043</a>

Jazyk výsledku

angličtina

Název v původním jazyce

ATR Prohibits Replication Catastrophe by Preventing Global Exhaustion of RPA

Popis výsledku v původním jazyce

ATR, activated by replication stress, protects replication forks locally and suppresses origin firing globally. Here, we show that these functions of ATR are mechanistically coupled. Although initially stable, stalled forks in ATR-deficient cells undergonucleus-wide breakage after unscheduled origin firing generates an excess of single-stranded DNA that exhausts the nuclear pool of RPA. Partial reduction of RPA accelerated fork breakage, and forced elevation of RPA was sufficient to delay such "replication catastrophe'' even in the absence of ATR activity. Conversely, unscheduled origin firing induced breakage of stalled forks even in cells with active ATR. Thus, ATR-mediated suppression of dormant origins shields active forks against irreversible breakage via preventing exhaustion of nuclear RPA. This study elucidates how replicating genomes avoid destabilizing DNA damage. Because cancer cells commonly feature intrinsically high replication stress, this study also provides a molecula

Název v anglickém jazyce

ATR Prohibits Replication Catastrophe by Preventing Global Exhaustion of RPA

Popis výsledku anglicky

ATR, activated by replication stress, protects replication forks locally and suppresses origin firing globally. Here, we show that these functions of ATR are mechanistically coupled. Although initially stable, stalled forks in ATR-deficient cells undergonucleus-wide breakage after unscheduled origin firing generates an excess of single-stranded DNA that exhausts the nuclear pool of RPA. Partial reduction of RPA accelerated fork breakage, and forced elevation of RPA was sufficient to delay such "replication catastrophe'' even in the absence of ATR activity. Conversely, unscheduled origin firing induced breakage of stalled forks even in cells with active ATR. Thus, ATR-mediated suppression of dormant origins shields active forks against irreversible breakage via preventing exhaustion of nuclear RPA. This study elucidates how replicating genomes avoid destabilizing DNA damage. Because cancer cells commonly feature intrinsically high replication stress, this study also provides a molecula

Druh

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

CEP obor

FD - Onkologie a hematologie

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

2013

Kód důvěrnosti údajů

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

Název periodika

Cell

ISSN

0092-8674

e-ISSN

—

Svazek periodika

155

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

1088-1103

Kód UT WoS článku

000327500600013

EID výsledku v databázi Scopus

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