Harmful R-loops are prevented via different cell cycle-specific mechanisms

• DOI: 10.1038/s41467-021-24737-x
• Publication Date: 2021-07-22T10:02:59Z
• Authors: Marta San Martin-...; María E. Soler-Oliva; María García-Rubio; Tatiana García-Muse; Andrés Aguilera
• Keywords: 0303 health sciences; Saccharomyces cerevisiae Proteins; Science; Q; Cell Cycle; Genes, Fungal; DNA Helicases; Nuclear Proteins; RNA, Fungal; Saccharomyces cerevisiae; Models, Biological; Article; Genomic Instability; 03 medical and health sciences; Mutation; R-Loop Structures; DNA, Fungal; RNA Helicases; DNA Damage; Transcription Factors

AbstractIdentifying how R-loops are generated is crucial to know how transcription compromises genome integrity. We show by genome-wide analysis of conditional yeast mutants that the THO transcription complex, prevents R-loop formation in G1 and S-phase, whereas the Sen1 DNA-RNA helicase prevents them only in S-phase. Interestingly, damage accumulates asymmetrically downstream of the replication fork in sen1 cells but symmetrically in the hpr1 THO mutant. Our results indicate that: R-loops form co-transcriptionally independently of DNA replication; that THO is a general and cell-cycle independent safeguard against R-loops, and that Sen1, in contrast to previously believed, is an S-phase-specific R-loop resolvase. These conclusions have important implications for the mechanism of R-loop formation and the role of other factors reported to affect on R-loop homeostasis.