Structural characterization of the interaction between BRCA1-BARD1 and RNA polymerase II

Veronika Klápšťová1,2, Kateřina Šedová1, Josef Houser1,2, Richard Štefl1,2, Marek Šebesta1

1Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic 

2National Center for Biomolecular Research, Faculty of Science, Masaryk University, Brno, Czech Republic

 

Transcription – a crucial process, which primarily generates messenger RNAs – competes for its substrate, DNA, with other processes, such as DNA repair. However, the principles underlying the crosstalk between the abovementioned processes remain poorly understood. The existing evidence indicates that the BRCA1-BARD1 complex, an early factor in the DNA damage response, is among the potential candidates for coordinating transcription and DNA repair. In our study, we investigated the molecular mechanism of the interaction between RNA polymerase II (RNAPII) and the BRCA1-BARD1 complex, as well as its functional consequence. Our data suggest that the BRCT repeat of BRCA1 binds the CTD, phosphorylated on Ser5, via the established mechanism. Moreover, we show that the interaction between the BRCT repeats and the hyperphosphorylated CTD is crucial for organisation of RNAPII into condensates with liquid-like properties. A subsequent analysis of disease-associated variants identified within the BRCT repeats supports our view that the observed condensation is indeed biologically relevant. Altogether, our data suggest that the BRCA1-BARD1 complex may coordinate transcription and DNA repair by organising RNAPII into transcription factories.