The molecular chaperone ALYREF promotes R-loop resolution and maintains genome stability
Unscheduled R-loops usually cause DNA damage and replication stress, and are therefore a major threat to genome stability. Several RNA processing factors, including the conserved THO complex and its associated RNA and DNA-RNA helicase UAP56, prevent R-loop accumulation in cells. Here, we investigate...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universidad de Sevilla (US) |
| Repositorio: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:idus.us.es:11441/166933 |
| Acceso en línea: | https://hdl.handle.net/11441/166933 https://doi.org/10.1016/j.jbc.2024.107996 |
| Access Level: | acceso abierto |
| Palabra clave: | ALYREF DNA-RNA helicase Genome instability R-loop TREX complex UAP56 |
| Sumario: | Unscheduled R-loops usually cause DNA damage and replication stress, and are therefore a major threat to genome stability. Several RNA processing factors, including the conserved THO complex and its associated RNA and DNA-RNA helicase UAP56, prevent R-loop accumulation in cells. Here, we investigate the function of ALYREF, an RNA export adapter associated with UAP56 and the THO complex, in R-loop regulation. We demonstrate that purified ALYREF promotes UAP56-mediated R-loop dissociation in vitro, and this stimulation is dependent on its interaction with UAP56 and R-loops. Importantly, we show that ALYREF binds DNA-RNA hybrids and R-loops. Consistently, ALYREF depletion causes R-loop accumulation and R-loop–mediated genome instability in cells. We propose that ALYREF, apart from its known role in RNA metabolism and export, is a key cellular R-loop coregulator, which binds R-loops and stimulates UAP56-driven resolution of unscheduled R-loops during transcription. |
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