Excessive reactive oxygen species induce transcription-dependent replication stress

Andrs, Martin; Stoy, Henriette; Boleslavska, Barbora; Chappidi, Nagaraja; Kanagaraj, Radhakrishnan; Nascakova, Zuzana; Menon, Shruti; Rao, Satyajeet; Oravetzova, Anna; Dobrovolna, Jana; Surendranath, Kalpana; Lopes, Massimo; Janscak, Pavel

doi:10.1038/s41467-023-37341-y

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Andrs, M., Stoy, H., Boleslavska, B., Chappidi, N., Kanagaraj, R., Nascakova, Z., Menon, S., Rao, S., Oravetzova, A., Dobrovolna, J., Surendranath, K., Lopes, M., & Janscak, P. (2023). Excessive reactive oxygen species induce transcription-dependent replication stress. Nature Communications, 14(1), 1791. https://doi.org/10.1038/s41467-023-37341-y

Abstract

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