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Excessive reactive oxygen species induce transcription-dependent replication stress
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SYSNO ASEP 0571218 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Excessive reactive oxygen species induce transcription-dependent replication stress Author(s) Andrš, Martin (UMG-J)
Stoy, H. (CH)
Boleslavská, Barbora (UMG-J)
Chappidi, N. (CH)
Kanagaraj, R. (GB)
Naščáková, Zuzana (UMG-J)
Menon, S. (CH)
Rao, S. (CH)
Oravetzová, Anna (UMG-J)
Dobrovolná, Jana (UMG-J) RID
Surendranath, K. (GB)
Lopes, M. (CH)
Janščák, Pavel (UMG-J) RIDNumber of authors 13 Article number 1791 Source Title Nature Communications. - : Nature Publishing Group
Roč. 14, č. 1 (2023)Number of pages 15 s. Language eng - English Country US - United States Keywords DNA-REPLICATION ; GENOMIC INSTABILITY ; FORK REVERSAL ; R-LOOPS ; DAMAGE ; ARCHITECTURE ; CONFLICTS ; YEAST OECD category Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology R&D Projects EF18_046/0016045 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2018129 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) GA22-08294S GA ČR - Czech Science Foundation (CSF) GX21-22593X GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support UMG-J - RVO:68378050 UT WOS 000961133600012 EID SCOPUS 85151316420 DOI 10.1038/s41467-023-37341-y Annotation 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. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2024 Electronic address https://www.nature.com/articles/s41467-023-37341-y
Number of the records: 1