RT Journal Article T1 Harmful R-loops are prevented via different cell cycle-specific mechanisms A1 San Martin-Alonso, Marta A1 Soler-Oliva, María E. A1 García-Rubio, María A1 García-Muse, Tatiana A1 Aguilera, Andrés K1 Cell Cycle K1 DNA Damage K1 DNA Helicases K1 Genomic Instability K1 Mutation K1 Nuclear Proteins K1 RNA, Fungal K1 Ciclo Celular K1 Daño del ADN K1 ADN Helicasas K1 Inestabilidad Genómica K1 Mutación K1 Proteínas Nucleares K1 ARN de Hongos AB Identifying 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. PB Springer Nature YR 2021 FD 2021-07-22 LK http://hdl.handle.net/10668/3470 UL http://hdl.handle.net/10668/3470 LA en NO San Martin-Alonso M, Soler-Oliva ME, García-Rubio M, García-Muse T, Aguilera A. Harmful R-loops are prevented via different cell cycle-specific mechanisms. Nature Communications. 2021;12(1):4451. DS RISalud RD May 11, 2025