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1000
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Abstract/Summary
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The BRCA1/BARD1 complex plays a key role in the repair of DNA double-strand breaks (DSBs) in both somatic cells and
germ cells. However, the underlying molecular mechanism by which this complex mediates DSB repair is not fully
understood. Here, we examined the XY body of male germ cells, where DSBs are accumulated. We show that the
recruitment of the BRCA1/BARD1 complex to the unsynapsed axis of the XY body is mediated by pre-ribosomal RNA
(pre-rRNA). Similarly, the BRCA1/BARD1 complex associates with pre-rRNA in somatic cells, which not only forms
nuclear foci in response to DSBs, but also targets the BRCA1/BARD1 complex to DSBs. The interactions between the
BRCT domains of the BRCA1/BARD1 complex and pre-rRNA induce liquid–liquid phase separations, which may be the
molecular basis of DSB-induced nuclear foci formation of the BRCA1/BARD1 complex. Moreover, cancer-associated
mutations in the BRCT domains of BRCA1 and BARD1 abolish their interactions with pre-rRNA. Pre-rRNA also mediates
BRCA1-dependent homologous recombination, and suppression of pre-rRNA biogenesis sensitizes cells to PARP
inhibitor treatment. Collectively, this study reveals that pre-rRNA is a functional partner of the BRCA1/BARD1 complex
in the DSB repair.
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