Excessive reactive oxygen species induce transcription-dependent replication stress
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F23%3A00571218" target="_blank" >RIV/68378050:_____/23:00571218 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/23:10467023
Result on the web
<a href="https://www.nature.com/articles/s41467-023-37341-y" target="_blank" >https://www.nature.com/articles/s41467-023-37341-y</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41467-023-37341-y" target="_blank" >10.1038/s41467-023-37341-y</a>
Alternative languages
Result language
angličtina
Original language name
Excessive reactive oxygen species induce transcription-dependent replication stress
Original language description
Elevated levels of reactive oxygen species (ROS) reduce replication fork velocity by causing dissociation of the TIMELESS-TIPIN complex from the replisome. Here, we show that ROS generated by exposure of human cells to the ribonucleotide reductase inhibitor hydroxyurea (HU) promote replication fork reversal in a manner dependent on active transcription and formation of co-transcriptional RNA:DNA hybrids (R-loops). The frequency of R-loop-dependent fork stalling events is also increased after TIMELESS depletion or a partial inhibition of replicative DNA polymerases by aphidicolin, suggesting that this phenomenon is due to a global replication slowdown. In contrast, replication arrest caused by HU-induced depletion of deoxynucleotides does not induce fork reversal but, if allowed to persist, leads to extensive R-loop-independent DNA breakage during S-phase. Our work reveals a link between oxidative stress and transcription-replication interference that causes genomic alterations recurrently found in human cancer.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10602 - Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature Communications
ISSN
2041-1723
e-ISSN
2041-1723
Volume of the periodical
14
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
1791
UT code for WoS article
000961133600012
EID of the result in the Scopus database
2-s2.0-85151316420