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

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.

SUBMITTER: San Martin-Alonso M

PROVIDER: S-EPMC8298424 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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

San Martin-Alonso Marta M Soler-Oliva María E ME García-Rubio María M García-Muse Tatiana T Aguilera Andrés A

Nature communications 20210722 1

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-trans ...[more]

PMID: 34294712

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Harmful R loops are prevented via different cell cycle specific mechanisms

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