Cañas, Juan CarlosGarcía-Rubio, María LuisaGarcía, AliciaAntequera, FranciscoGómez-González, BelénAguilera, Andrés2023-05-032023-05-032022http://hdl.handle.net/10668/19782The stability of the genome is occasionally challenged by the formation of DNA-RNA hybrids and R-loops, which can be influenced by the chromatin context. This is mainly due to the fact that DNA-RNA hybrids hamper the progression of replication forks, leading to fork stalling and, ultimately, DNA breaks. Through a specific screening of chromatin modifiers performed in the yeast Saccharomyces cerevisiae, we have found that the Rtt109 histone acetyltransferase is involved in several steps of R-loop-metabolism and their associated genetic instability. On the one hand, Rtt109 prevents DNA-RNA hybridization by the acetylation of histone H3 lysines 14 and 23 and, on the other hand, it is involved in the repair of replication-born DNA breaks, such as those that can be caused by R-loops, by acetylating lysines 14 and 56. In addition, Rtt109 loss renders cells highly sensitive to replication stress in combination with R-loop-accumulating THO-complex mutants. Our data evidence that the chromatin context simultaneously influences the occurrence of DNA-RNA hybrid-associated DNA damage and its repair, adding complexity to the source of R-loop-associated genetic instability.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/DNA–RNA hybridsR-loopsgenetic instabilityhistone acetylationsister-chromatid recombinationAcetylationChromatinDNA ReplicationGenomic InstabilityHistone AcetyltransferasesHomeostasisR-Loop StructuresRNASaccharomyces cerevisiaeSaccharomyces cerevisiae Proteinsresearch article35866610open access10.1093/genetics/iyac1081943-2631PMC9434296https://academic.oup.com/genetics/article-pdf/222/1/iyac108/45616901/iyac108.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9434296/pdf