ATR Prohibits Replication Catastrophe by Preventing Global Exhaustion of RPA

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

ATR Prohibits Replication Catastrophe by Preventing Global Exhaustion of RPA

Original language description

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

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FD - Oncology and haematology

OECD FORD branch

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Project

<a href="/en/project/ED0030%2F01%2F01" target="_blank" >ED0030/01/01: Biomedicine for regional development and human resources</a><br>

Continuities

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

Publication year

2013

Confidentiality

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

Name of the periodical

Cell

ISSN

0092-8674

e-ISSN

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Volume of the periodical

155

Issue of the periodical within the volume

5

Country of publishing house

US - UNITED STATES

Number of pages

16

Pages from-to

1088-1103

UT code for WoS article

000327500600013

EID of the result in the Scopus database

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