2019-06-132019-06-132017Salas Armenteros, I., Pérez Calero, C., Bayona Feliu, A., Tumini, E., Luna Varo, R.M. y Aguilera López, A. (2017). Human THO–Sin3A interaction reveals new mechanisms to prevent R-loops that cause genome instability. EMBO Journal, 36 (23), 3532-3547.0261-41891460-2075https://hdl.handle.net/11441/87419R-loops, formed by co-transcriptional DNA–RNA hybrids and a displaced DNA single strand (ssDNA), fulfill certain positive regulatory roles but are also a source of genomic instability. One key cellular mechanism to prevent R-loop accumulation centers on the conserved THO/TREX complex, an RNA-binding factor involved in transcription elongation and RNA export that contributes to messenger ribonucleoprotein (mRNP) assembly, but whose precise function is still unclear. To understand how THO restrains harmful R-loops, we searched for new THO-interacting factors. We found that human THO interacts with the Sin3A histone deacetylase complex to suppress co-transcriptional R-loops, DNA damage, and replication impairment. Functional analyses show that histone hypo-acetylation prevents accumulation of harmful R-loops and RNA-mediated genomic instability. Diminished histone deacetylase activity in THO- and Sin3A-depleted cell lines correlates with increased R-loop formation, genomic instability, and replication fork stalling. Our study thus uncovers physical and functional crosstalk between RNA-binding factors and chromatin modifiers with a major role in preventing R-loop formation and RNA-mediated genome instability.application/pdfengAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/DNA–RNA hybridsGenome instabilityHistone acetylationSin3A deacetylaseTHO/TREXinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccess10.15252/embj.201797208