ALYREF binds to poly-ADP-ribose at double strand breaks impairing repair in tumoral cells

Abstract DNA–RNA hybrids cause genome instability by promoting transcription-replication conflicts. However, as they are stimulated at double-stranded breaks (DSBs), they can also impact DSB repair. We investigated whether the RNA chaperon ALYREF and its RNA helicase partner UAP56/DDX39B, both of which regulate RNA biogenesis and R-loops, also act at DSBs. We found that ALYREF, but not UAP56/DDX39B, is recruited to DSBs. Recruitment is partially dependent on transcription and hybrids, and fully dependent on polyADP-ribose (PAR). Consistently, we show that ALYREF, but not UAP56/DDX39B, binds PAR in vitro. Notably, ALYREF overexpression delays DSB repair by retaining PAR levels and interfering with the loading dynamics of early DSB repair factors that regulate DNA resection. Interestingly, we detect high ALYREF levels in numerous cancer subtypes by database analysis. We propose that ALYREF, when overexpressed, induces genome instability in tumoral cells by interfering with DSB repair.

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Publication Details

Journal
EMBO Reports
Published
2026-10-19
DOI
https://doi.org/10.1038/s44319-026-00963-6
Primary Topic
DNA Repair Mechanisms
Type
article
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article

ALYREF binds to poly-ADP-ribose at double strand breaks impairing repair in tumoral cells

Sonia I. Barroso, Xiaoyu Xue, Andrés Aguilera, Belén Gómez‐González et al.
EMBO Reports
DNA Repair Mechanisms
article

ALYREF binds to poly-ADP-ribose at double strand breaks impairing repair in tumoral cells

Sonia I. Barroso, Xiaoyu Xue, Andrés Aguilera, Belén Gómez‐González, Rosa Luna, Cristina Guillén-Mendoza, Mar Bustamante-Sequeiros, Aleix Bayona‐Feliú, Sara Priego Moreno, Sonia de Regules Silva, Lillian Eliaz, Iván Núñez-Martín, Leire Asua Intxausti, Noelia Gil-Lanza, Sandra Trujillo-Sierra
article en

Abstract

Abstract DNA–RNA hybrids cause genome instability by promoting transcription-replication conflicts. However, as they are stimulated at double-stranded breaks (DSBs), they can also impact DSB repair. We investigated whether the RNA chaperon ALYREF and its RNA helicase partner UAP56/DDX39B, both of which regulate RNA biogenesis and R-loops, also act at DSBs. We found that ALYREF, but not UAP56/DDX39B, is recruited to DSBs. Recruitment is partially dependent on transcription and hybrids, and fully dependent on polyADP-ribose (PAR). Consistently, we show that ALYREF, but not UAP56/DDX39B, binds PAR in vitro. Notably, ALYREF overexpression delays DSB repair by retaining PAR levels and interfering with the loading dynamics of early DSB repair factors that regulate DNA resection. Interestingly, we detect high ALYREF levels in numerous cancer subtypes by database analysis. We propose that ALYREF, when overexpressed, induces genome instability in tumoral cells by interfering with DSB repair.

EMBO Reports
Texas State University (US), Centro Andaluz de Biología Molecular y Medicina Regenerativa (ES), Universitat de Barcelona (ES), Universidad de Sevilla (ES), Universidad Pablo de Olavide (ES)
Openalex Percentile: Top 23%
DNA Repair Mechanisms
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