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

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2021-07-22

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San Martin-Alonso, Marta
Soler-Oliva, María E.
García-Rubio, María
García-Muse, Tatiana
Aguilera, Andrés

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Springer Nature
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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.

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Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Cycle
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Damage
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Acid Anhydride Hydrolases::Adenosine Triphosphatases::DNA Helicases
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNA::DNA, Fungal
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genomic Instability
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Biological
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nuclear Proteins
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Nucleotidyltransferases::RNA Nucleotidyltransferases::RNA Helicases
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Fungal
Medical Subject Headings::Organisms::Eukaryota::Fungi::Ascomycota::Saccharomycetales::Saccharomyces::Saccharomyces cerevisiae
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Fungal Proteins::Saccharomyces cerevisiae Proteins
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors

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Keywords

Cell Cycle, DNA Damage, DNA Helicases, Genomic Instability, Mutation, Nuclear Proteins, RNA, Fungal, Ciclo Celular, Daño del ADN, ADN Helicasas, Inestabilidad Genómica, Mutación, Proteínas Nucleares, ARN de Hongos

Citation

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.