Yinghua Chen

BRCA1 is a tumor suppressor gene mutated in a high percentage of hereditary breast and ovarian cancers. BRCA1 forms distinct complexes involved in cellular pathways such as DNA repair, transcription, cell cycle regulation, and protein ubiquitination. We are interested in the structure and function of the BRCA1 protein, one of largest human proteins (1863 amino acid residues). Previous structural studies have characterized the N-terminal and C-terminal domains of this protein, but the remaining 1500 amino acid interior region reveals no statistically significant homology to proteins of known structure. However, this region interacts directly with many proteins. To identify the domains within this region of the BRCA1 protein, we have used a bioinformatics approach and identified several candidates. To determine the structures of these domains, we are using automated high throughput protein overexpression techniques to generate corresponding soluble polypeptides. In addition, we are working on BRCA1 protein complex dynamics and structural regulation of BRCA1 by protein interactions and modifications.