BGL3 lncRNA mediates retention of the BRCA1/BARD1 complex at DNA damage sites.
EMBO J
; 39(12): e104133, 2020 06 17.
Article
en En
| MEDLINE
| ID: mdl-32347575
ABSTRACT
Long non-coding RNAs (lncRNAs) are emerging regulators of genomic stability and human disease. However, the molecular mechanisms by which nuclear lncRNAs directly contribute to DNA damage responses remain largely unknown. Using RNA antisense purification coupled with quantitative mass spectrometry (RAP-qMS), we found that the lncRNA BGL3 binds to PARP1 and BARD1, exhibiting unexpected roles in homologous recombination. Mechanistically, BGL3 is recruited to DNA double-strand breaks (DSBs) by PARP1 at an early time point, which requires its interaction with the DNA-binding domain of PARP1. BGL3 also binds the C-terminal BRCT domain and an internal region (amino acids 127-424) of BARD1, which mediates interaction of the BRCA1/BARD1 complex with its binding partners such as HP1γ and RAD51, resulting in BRCA1/BARD1 retention at DSBs. Cells depleted for BGL3 displayed genomic instability and were sensitive to DNA-damaging reagents. Overall, our findings underscore the biochemical versatility of RNA as a mediator molecule in the DNA damage response pathway, which affects the accumulation of BRCA1/BARD1 at DSBs.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
Proteína BRCA1
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Proteínas Supresoras de Tumor
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Ubiquitina-Proteína Ligasas
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Complejos Multiproteicos
/
Roturas del ADN de Doble Cadena
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ARN Largo no Codificante
Límite:
Humans
Idioma:
En
Revista:
EMBO J
Año:
2020
Tipo del documento:
Article
País de afiliación:
China