San Martin-Alonso, MartaSoler-Oliva, María E.García-Rubio, MaríaGarcía-Muse, TatianaAguilera, Andrés2022-03-082022-03-082021-07-22San 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.http://hdl.handle.net/10668/3470Identifying 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Cell CycleDNA DamageDNA HelicasesGenomic InstabilityMutationNuclear ProteinsRNA, FungalCiclo CelularDaño del ADNADN HelicasasInestabilidad GenómicaMutaciónProteínas NuclearesARN de HongosMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell CycleMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA DamageMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Acid Anhydride Hydrolases::Adenosine Triphosphatases::DNA HelicasesMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNA::DNA, FungalMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genomic InstabilityMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, BiologicalMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::MutationMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nuclear ProteinsMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Nucleotidyltransferases::RNA Nucleotidyltransferases::RNA HelicasesMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, FungalMedical Subject Headings::Organisms::Eukaryota::Fungi::Ascomycota::Saccharomycetales::Saccharomyces::Saccharomyces cerevisiaeMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Fungal Proteins::Saccharomyces cerevisiae ProteinsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factorsresearch article34294712Acceso abierto10.1038/s41467-021-24737-x2041-1723PMC8298424