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...
| Authors: | , , , , , , , , |
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| Format: | article |
| Status: | Published version |
| Publication Date: | 2024 |
| Country: | España |
| Institution: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repository: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/378587 |
| Online Access: | http://hdl.handle.net/10261/378587 https://api.elsevier.com/content/abstract/scopus_id/85211055351 |
| Access Level: | Open access |
| Keyword: | ALYREF DNA-RNA helicase R-loop TREX complex UAP56 Genome instability |
| Summary: | 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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