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

Marta San Martin-Alonso, María E. Soler-Oliva, María García-Rubio, Tatiana García-Muse () and Andrés Aguilera ()
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Marta San Martin-Alonso: Universidad de Sevilla-CSIC-UPO
María E. Soler-Oliva: Universidad de Sevilla-CSIC-UPO
María García-Rubio: Universidad de Sevilla-CSIC-UPO
Tatiana García-Muse: Universidad de Sevilla-CSIC-UPO
Andrés Aguilera: Universidad de Sevilla-CSIC-UPO

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-24737-x

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