Mutation in the BCRA2 gene has been identified as a genetic marker that indicates a predisposition for the development of breast cancer. Understanding how this tumor suppressor protein functions is vital in understanding disease progression. Until now, researchers have been limited in their studies of protein function due to inability to purify a complete BCRA2 protein and had to rely on studying protein fragments. In a of Nature Structural & Molecular Biology, UNC researcher publicationJack Griffith and colleges have been able to purify a full length BCRA2 protein from HeLa cells using human bacterial artificial chromosomes (BACs).
Studies using the full length protein demonstrate that BRCA 2 protein can occur as a monomer or dimer, and binds selectively to single stranded DNA (ssDNA), ssDNA in duplexes and in replication forks. Data produced also indicates that the BCRA protein directs the binding of the RAD 51recombinase to ssDNA and reduces its binding to double stranded DNA. It was also implicated in stimulating RAD51-mediated strand repair.
Jack Griffith is renowned for his work pioneering the application of electron microscopy to the study of protein-nucleic acid interactions and has received numerous awards for those ongoing contributions. His methods provided the first ever EM images of specific protein–DNA complexes. Since then he has applied these techniques to numerous systems including the organization of nucleosomes in chromatin, DNA replication complexes, ribozymes and telomeres, to name a few. Dr Griffith has been a Kenan Distinguished Professor at UNC since 2002.