Martina Foglizzo
University of Leeds
Thursday 28 September 2023, 17.00 Cyprus time
BRCA1-BARD1 bridges across nucleosomes and “inchworms” on chromatin, using multiple interaction modules
ABSTRACT
Cellular responses to DNA double strand breaks (DSBs) are dependent on a set of nucleosome “signposts” that are written, read and erased by highly specialised multi-protein complexes. The tumour suppressor and E3 ubiquitin ligase BRCA1-BARD1 is recruited to damaged chromatin via recognition of ubiquitylated Lys13/Lys15 on histone H2A and unmethylated Lys20 on H4. Interactions of BRCA1-BARD1 with the nucleosome surface promotes the covalent attachment of ubiquitin to Lys125/Lys127/Lys129 on H2A, thus ensuring a timely DNA repair. I will discuss our latest work (and that of others) using recombinant expression systems alongside with biochemical/biophysical and structural techniques that shed light into how the BRCA1-BARD1 complex recognises and modifies chromatin, and how its DNA repair and enzymatic activities are regulated.
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