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BGL3 lncRNA mediates retention of the BRCA1/BARD1 complex at DNA damage sites
Author(s) -
Hu Zhaohua,
Mi Shaojie,
Zhao Ting,
Peng Changmin,
Peng Yihan,
Chen Lulu,
Zhu Wenge,
Yao Yi,
Song Qibin,
Li Xiangpan,
Li Xinzhi,
Jia Chenxi,
Pei Huadong
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019104133
Subject(s) - biology , dna damage , dna , genetics , computational biology , microbiology and biotechnology
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.