Artículo
Human THO–Sin3A interaction reveals new mechanisms to prevent R-loops that cause genome instability
Autor/es | Salas Armenteros, Irene
Pérez Calero, Carmen Bayona Feliu, Aleix Tumini, Emanuela Luna Varo, Rosa María Aguilera López, Andrés |
Departamento | Universidad de Sevilla. Departamento de Genética |
Fecha de publicación | 2017 |
Fecha de depósito | 2019-06-13 |
Publicado en |
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Resumen | R-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-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. |
Identificador del proyecto | ERC2014 AdG669898 TARLOOP
BFU2013-42918-P BFU2016-75058-P BIO1238 |
Cita | Salas 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. |
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