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Título : Harmful R-loops are prevented via different cell cycle-specific mechanisms.
Autor : San Martin-Alonso, Marta
Soler-Oliva, María E
García-Rubio, María
García-Muse, Tatiana
Aguilera, Andrés
MeSH: Cell Cycle
DNA Damage
DNA Helicases
DNA, Fungal
Genes, Fungal
Genomic Instability
Models, Biological
Mutation
Nuclear Proteins
R-Loop Structures
RNA Helicases
RNA, Fungal
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Transcription Factors
Fecha de publicación : 22-jul-2021
Abstract: 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.
URI: http://hdl.handle.net/10668/19504
DOI: 10.1038/s41467-021-24737-x
Aparece en las colecciones: Producción 2020

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