RT Journal Article
T1 DNA-RNA hybrids at DSBs interfere with repair by homologous recombination
A1 Ortega, Pedro
A1 Mérida-Cerro, José Antonio
A1 Rondón, Ana G.
A1 Gómez-González, Belén
A1 Aguilera, Andrés
K1 Homologous recombination
K1 DNA
K1 RNA
K1 Hybrids
K1 Double-strand breaks
K1 Recombinación homóloga
K1 ADN
K1 ARN
K1 Quimera
K1 Roturas del ADN de doble cadena
AB DNA double-strand breaks (DSBs) are the most harmful DNA lesions and their repair is crucial for cell viability and genome integrity. The readout of DSB repair may depend on whether DSBs occur at transcribed versus non-transcribed regions. Some studies have postulated that DNA-RNA hybrids form at DSBs to promote recombinational repair, but others have challenged this notion. To directly assess whether hybrids formed at DSBs promote or interfere with the recombinational repair, we have used plasmid and chromosomal-based systems for the analysis of DSB-induced recombination in Saccharomyces cerevisiae. We show that, as expected, DNA-RNA hybrid formation is stimulated at DSBs. In addition, mutations that promote DNA-RNA hybrid accumulation, such as hpr1∆ and rnh1∆ rnh201∆, cause high levels of plasmid loss when DNA breaks are induced at sites that are transcribed. Importantly, we show that high levels or unresolved DNA-RNA hybrids at the breaks interfere with their repair by homologous recombination. This interference is observed for both plasmid and chromosomal recombination and is independent of whether the DSB is generated by endonucleolytic cleavage or by DNA replication. These data support a model in which DNA-RNA hybrids form fortuitously at DNA breaks during transcription and need to be removed to allow recombinational repair, rather than playing a positive role.
PB eLife Sciences Publications
YR 2021
FD 2021-07-08
LK http://hdl.handle.net/10668/4186
UL http://hdl.handle.net/10668/4186
LA en
NO Ortega P, Mérida-Cerro JA, Rondón AG, Gómez-González B, Aguilera A. DNA-RNA hybrids at DSBs interfere with repair by homologous recombination. Elife. 2021 Jul 8;10:e69881
DS RISalud
RD Apr 18, 2025