Profiling BRCA1-BRCT interactions and their functional relevance at amino acid resolution.

ABSTRACT: BRCA1 (breast cancer-associated protein 1) plays a central role in homologous recombination (HR) through interactions with multiple proteins across its various domains. The C-terminal BRCT domains bind HR regulators such as ABRAXAS1, CtIP, and BRIP1, each contributing to distinct, sometimes opposing, functions. While pathogenic mutations frequently cluster within the canonical BRCT phospho-binding pocket, the broader mutational landscape and its functional consequences remain poorly understood. Here, we used a site-saturation mutagenesis library of the BRCT domains to test >4,000 single-residue variants for their ability to bind ABRAXAS1 and CtIP. Using a yeast two-hybrid screen, we systematically assessed these interactions and validated key findings in mammalian cells. The resulting inte

SUBMITTER: Mangkusaputra V 

PROVIDER: S-EPMC12448885 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature