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Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51
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SFPQ Promotes Homologous Recombination via mRNA Stabilization of RAD51 and Its Paralogs
Sofia Gotthold1, Keile R Hansen2, Andrew N Brown2
1Interdisciplinary Program in Quantitative Biosciences. University of California, Santa Barbara, CA 93106, USA.
Biorxiv : the Preprint Server for Biology
|September 18, 2025
Summary
The splicing factor SFPQ stabilizes RAD51 expression, influencing DNA repair pathways like homologous recombination (HR). This occurs by maintaining mRNA stability, not direct interaction with DNA breaks, impacting genome stability.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- DNA double-strand breaks (DSBs) are repaired via non-homologous end joining (NHEJ) or homologous recombination (HR).
- Identifying non-canonical factors influencing DSB repair outcomes is crucial for understanding genome stability.
- The splicing factor SFPQ has been implicated in DSB repair, with prior studies suggesting its localization to DSBs.
Purpose of the Study:
- To identify novel factors affecting DSB repair outcomes.
- To elucidate the mechanism by which SFPQ influences DSB repair.
- To investigate the role of SFPQ in homologous recombination (HR) and its interaction with DNA damage response pathways.
Main Methods:
- Pooled genetic screening to identify factors influencing DSB repair.
- Depletion studies to assess the impact of SFPQ on DNA repair.
- Analysis of RAD51 and its paralog expression levels.
- Investigation of SFPQ localization in response to DNA damage.
Main Results:
- SFPQ depletion was found to alter DSB repair outcomes, specifically impacting HR.
- Contrary to previous reports, SFPQ was not observed to localize to DSBs.
- SFPQ was shown to stabilize the expression of RAD51 and its paralogs independently of p53 activation or DNA damage.
- This stabilization mechanism involves maintaining RAD51 paralog mRNA stability.
Conclusions:
- SFPQ contributes to constitutive DSB repair by stabilizing RAD51 paralog mRNA.
- SFPQ influences genome stability through indirect mechanisms, independent of direct DSB interaction.
- RNA-binding proteins can play significant roles in genome stability through post-transcriptional regulation.
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