Multifactorial contributions to an acute DNA damage response by BRCA1/BARD1-containing complexes.
The BRCA1 gene product and its stoichiometric binding partner, BARD1, play a vital role in the cellular response to DNA damage. However, how they acquire specific biochemical functions after DNA damage is poorly understood. Following exposure to genotoxic stress, DNA damage-specific interactions were observed between BRCA1/BARD1 and the DNA damage-response proteins, TopBP1 and Mre11/Rad50/NBS1. Two distinct DNA damage-dependent super complexes emerged; their activation was dependent, in part, on the actions of specific checkpoint kinases, and each super complex contributed to a distinctive aspect of the DNA damage response. The results support a new, multifactorial model that describes how genotoxic stress enables BRCA1 to execute a diverse set of DNA damage-response functions.
Pubmed ID: 16391231 RIS Download
BRCA1 Protein | Carrier Proteins | Cell Cycle | Cell Cycle Proteins | Cell Line, Tumor | DNA Damage | DNA Repair | DNA Repair Enzymes | DNA-Binding Proteins | Humans | Nuclear Proteins | Protein Binding | Tumor Suppressor Proteins | Ubiquitin-Protein Ligases